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<script type="text/javascript" src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/jr.boots.min.js"> </script><title>Mucopolysaccharidosis Type III - GeneReviews® - NCBI Bookshelf</title>
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<meta name="citation_title" content="Mucopolysaccharidosis Type III">
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<meta name="citation_publisher" content="University of Washington, Seattle">
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<meta name="citation_date" content="2019/09/19">
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<meta name="citation_author" content="Victoria F Wagner">
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<meta name="citation_author" content="Hope Northrup">
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<meta name="citation_pmid" content="31536183">
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<meta name="citation_fulltext_html_url" content="https://www.ncbi.nlm.nih.gov/books/NBK546574/">
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<meta name="citation_keywords" content="MPS III">
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<meta name="citation_keywords" content="Sanfilippo Syndrome">
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<meta name="citation_keywords" content="Sanfilippo Syndrome">
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<meta name="citation_keywords" content="MPS III">
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<meta name="citation_keywords" content="MPS IIIB">
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<meta name="citation_keywords" content="MPS IIIC">
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<meta name="citation_keywords" content="MPS IIID">
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<meta name="citation_keywords" content="MPS IIIA">
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<meta name="citation_keywords" content="Alpha-N-acetylglucosaminidase">
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<meta name="citation_keywords" content="Heparan-alpha-glucosaminide N-acetyltransferase">
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<meta name="citation_keywords" content="N-acetylglucosamine-6-sulfatase">
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<meta name="citation_keywords" content="N-sulphoglucosamine sulphohydrolase">
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<meta name="citation_keywords" content="GNS">
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<meta name="citation_keywords" content="HGSNAT">
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<meta name="citation_keywords" content="Mucopolysaccharidosis Type III">
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<meta name="DC.Title" content="Mucopolysaccharidosis Type III">
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<meta name="DC.Publisher" content="University of Washington, Seattle">
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<meta name="DC.Contributor" content="Victoria F Wagner">
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<meta name="DC.Contributor" content="Hope Northrup">
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<meta name="DC.Date" content="2019/09/19">
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<meta name="DC.Identifier" content="https://www.ncbi.nlm.nih.gov/books/NBK546574/">
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<meta name="description" content="Mucopolysaccharidosis type III (MPS III) is a multisystem lysosomal storage disease characterized by progressive central nervous system degeneration manifest as severe intellectual disability (ID), developmental regression, and other neurologic manifestations including autism spectrum disorder (ASD), behavioral problems, and sleep disturbances. Disease onset is typically before age ten years. Disease course may be rapidly or slowly progressive; some individuals with an extremely attenuated disease course present in mid-to-late adulthood with early-onset dementia with or without a history of ID. Systemic manifestations can include musculoskeletal problems (joint stiffness, contractures, scoliosis, and hip dysplasia), hearing loss, respiratory tract and sinopulmonary infections, and cardiac disease (valvular thickening, defects in the cardiac conduction system). Neurologic decline is seen in all affected individuals; however, clinical severity varies within and among the four MPS III subtypes (defined by the enzyme involved) and even among members of the same family. Death usually occurs in the second or third decade of life secondary to neurologic regression or respiratory tract infections.">
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<meta name="og:title" content="Mucopolysaccharidosis Type III">
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<meta name="og:description" content="Mucopolysaccharidosis type III (MPS III) is a multisystem lysosomal storage disease characterized by progressive central nervous system degeneration manifest as severe intellectual disability (ID), developmental regression, and other neurologic manifestations including autism spectrum disorder (ASD), behavioral problems, and sleep disturbances. Disease onset is typically before age ten years. Disease course may be rapidly or slowly progressive; some individuals with an extremely attenuated disease course present in mid-to-late adulthood with early-onset dementia with or without a history of ID. Systemic manifestations can include musculoskeletal problems (joint stiffness, contractures, scoliosis, and hip dysplasia), hearing loss, respiratory tract and sinopulmonary infections, and cardiac disease (valvular thickening, defects in the cardiac conduction system). Neurologic decline is seen in all affected individuals; however, clinical severity varies within and among the four MPS III subtypes (defined by the enzyme involved) and even among members of the same family. Death usually occurs in the second or third decade of life secondary to neurologic regression or respiratory tract infections.">
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class="wsprkl btn" title="Jump to next match">▶</a></nav></nav></div><div id="jr-epub-interstitial" class="hidden"></div><div id="jr-content"><article data-type="main"><div class="main-content lit-style" itemscope="itemscope" itemtype="http://schema.org/CreativeWork"><div class="meta-content fm-sec"><div class="fm-sec"><h1 id="_NBK546574_"><span class="title" itemprop="name">Mucopolysaccharidosis Type III</span></h1><div itemprop="alternativeHeadline" class="subtitle whole_rhythm">Synonyms: MPS III, Sanfilippo Syndrome</div><p class="contribs">Wagner VF, Northrup H.</p><p class="fm-aai"><a href="#_NBK546574_pubdet_">Publication Details</a></p><p><em>Estimated reading time: 29 minutes</em></p></div></div><div class="jig-ncbiinpagenav body-content whole_rhythm" data-jigconfig="allHeadingLevels: ['h2'],smoothScroll: false" itemprop="text"><div id="mps3.Summary" itemprop="description"><h2 id="_mps3_Summary_">Summary</h2><div><h4 class="inline">Clinical characteristics.</h4><p>Mucopolysaccharidosis type III (MPS III) is a multisystem lysosomal storage disease characterized by progressive central nervous system degeneration manifest as severe intellectual disability (ID), developmental regression, and other neurologic manifestations including autism spectrum disorder (ASD), behavioral problems, and sleep disturbances. Disease onset is typically before age ten years. Disease course may be rapidly or slowly progressive; some individuals with an extremely attenuated disease course present in mid-to-late adulthood with early-onset dementia with or without a history of ID. Systemic manifestations can include musculoskeletal problems (joint stiffness, contractures, scoliosis, and hip dysplasia), hearing loss, respiratory tract and sinopulmonary infections, and cardiac disease (valvular thickening, defects in the cardiac conduction system). Neurologic decline is seen in all affected individuals; however, clinical severity varies within and among the four MPS III subtypes (defined by the enzyme involved) and even among members of the same family. Death usually occurs in the second or third decade of life secondary to neurologic regression or respiratory tract infections.</p></div><div><h4 class="inline">Diagnosis/testing.</h4><p>The diagnosis of MPS III is established in a proband with suggestive clinical and laboratory findings in whom either biallelic pathogenic variants in one of four genes (<i>GNS</i>, <i>HGSNAT</i>, <i>NAGLU</i>, and <i>SGSH</i>) or deficiency of the respective lysosomal enzyme has been identified.</p></div><div><h4 class="inline">Management.</h4><p><i>Treatment of manifestations:</i> Supportive therapies for neurodevelopmental delays, hearing loss, and visual impairment; medications (rather than behavioral therapy) for psychiatric/behavioral issues; physical therapy and/or orthopedic management of musculoskeletal manifestations; and management as prescribed by consulting specialists for seizures, cardiac involvement, sleep disorders, feeding difficulties.</p><p><i>Surveillance:</i> Routine monitoring of: developmental capabilities and educational needs, destructive or disruptive behaviors; musculoskeletal involvement; hearing; cardiac involvement.</p><p><i>Agents/circumstances to avoid:</i> Procedures requiring anesthesia in centers ill-equipped or inexperienced in caring for patients with complex airway-management issues; hip surgery (due to high risk of osteonecrosis of the femoral head); environments not adapted to minimize risk from unpredictable behaviors.</p><p><i>Therapies under investigation:</i> Despite ongoing research for a variety of therapeutic options, no treatments are currently clinically available for treatment of the primary manifestations of MPS III.</p></div><div><h4 class="inline">Genetic counseling.</h4><p>MPS III is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Once the MPS III-causing pathogenic variants have been identified in an affected family member, carrier testing for at-risk relatives, prenatal testing for a pregnancy at increased risk, and preimplantation genetic testing are possible.</p></div></div><div id="mps3.GeneReview_Scope"><h2 id="_mps3_GeneReview_Scope_"><i>GeneReview</i> Scope</h2><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figmps3Td"><a href="/books/NBK546574/table/mps3.Td/?report=objectonly" target="object" title="Table" class="img_link icnblk_img" rid-ob="figobmps3Td"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="mps3.Td"><a href="/books/NBK546574/table/mps3.Td/?report=objectonly" target="object" rid-ob="figobmps3Td">Table</a></h4></div></div></div><div id="mps3.Diagnosis"><h2 id="_mps3_Diagnosis_">Diagnosis</h2><p>Formal diagnostic criteria for mucopolysaccharidosis type III (MPS III) have not been established.</p><div id="mps3.Suggestive_Findings"><h3>Suggestive Findings</h3><p>MPS III <b>should be suspected</b> in individuals with the following clinical findings and supportive laboratory or imaging findings.</p><p>
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<b>Clinical findings</b>
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</p><ul><li class="half_rhythm"><div><b>Age 1-3 years.</b> Language and motor delays</div></li><li class="half_rhythm"><div>
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<b>Age 3-10 years</b>
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</div><ul><li class="half_rhythm"><div>Language and motor delays</div></li><li class="half_rhythm"><div>Behavioral problems including hyperactivity and aggressive or defiant behaviors</div></li><li class="half_rhythm"><div>Sleep disturbances</div></li></ul></li><li class="half_rhythm"><div>
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<b>Age ≥10 years</b>
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</div><ul><li class="half_rhythm"><div>Intellectual disability</div></li><li class="half_rhythm"><div>Progressive developmental regression including loss of toilet training, language (if acquired), and motor skills</div></li><li class="half_rhythm"><div>Seizures</div></li><li class="half_rhythm"><div>Gait disorders</div></li></ul></li><li class="half_rhythm"><div>
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<b>General findings</b>
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</div><ul><li class="half_rhythm"><div>Coarse facies</div></li><li class="half_rhythm"><div>Thick hair and hirsutism</div></li><li class="half_rhythm"><div>Hepatosplenomegaly</div></li><li class="half_rhythm"><div>Joint stiffness</div></li><li class="half_rhythm"><div>Hearing loss</div></li><li class="half_rhythm"><div>Frequent upper-respiratory and ear infections</div></li><li class="half_rhythm"><div>Inguinal and/or umbilical hernias</div></li></ul></li></ul><p>Note: Clinical findings alone are not diagnostic and may vary by disease severity.</p><p><b>Supportive laboratory findings.</b> Analysis of urinary glycosaminoglycans (GAG) (i.e., heparan sulfate) may be quantitative (measurement of total urinary GAG amount) or qualitative (GAG electrophoresis to analyze specific GAGs present in the urine).</p><ul><li class="half_rhythm"><div>While quantitative and qualitative analysis of GAGs cannot diagnose specific lysosomal enzyme deficiencies, including MPS III, an abnormality in either quantitative or qualitative GAG analysis is suggestive of an MPS disorder.</div></li><li class="half_rhythm"><div>GAG electrophoresis can assist in excluding and including certain MPS disorders; however, definitive diagnosis requires additional testing (see <a href="#mps3.Establishing_the_Diagnosis">Establishing the Diagnosis</a>).</div></li><li class="half_rhythm"><div>Both methods of urinary GAG analysis have reduced sensitivity, especially if urine is dilute. Normal results on urinary GAG analysis cannot rule out an MPS disorder, particularly in the case of MPS III.</div></li></ul><p>
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<b>Imaging findings</b>
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</p><ul><li class="half_rhythm"><div><b>Radiographs.</b> Skeletal survey reveals mild signs of dysostosis multiplex (e.g., thickened "oar-shaped" ribs, scoliosis, kyphosis, misshaped or hypoplastic vertebral bodies, thickened diploic space), particularly in older children with a rapidly progressing form. Hip deformities such as acetabular dysplasia and osteonecrosis of the femoral head are also observed.</div></li><li class="half_rhythm"><div>
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<b>MRI</b>
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</div><ul><li class="half_rhythm"><div>Brain MRI demonstrates abnormalities such as white matter alterations (diffuse prolonged T<sub>1</sub> and T<sub>2</sub> relaxation times), enlarged subarachnoid and perivascular spaces, ventriculomegaly, and widening of the cortical sulci consistent with diffuse cerebral atrophy.</div></li><li class="half_rhythm"><div>Spine MRI reveals spinal stenosis or spinal cord compression that can lead to narrowing of the central canal.</div></li></ul></li><li class="half_rhythm"><div><b>Echocardiogram</b> often exhibits valvular anomalies including mitral or aortic valve thickening, mitral or aortic regurgitation, and mitral valve prolapse.</div></li></ul><p>Note: These findings may not be present in early life, may vary by disease severity, and are not specific to MPS III.</p></div><div id="mps3.Establishing_the_Diagnosis"><h3>Establishing the Diagnosis</h3><p>The diagnosis of MPS III <b>is established</b> in a proband with suggestive clinical and laboratory findings in whom either biallelic pathogenic variants in one of four genes (<i>GNS</i>, <i>HGSNAT</i>, <i>NAGLU</i>, and <i>SGSH</i>) (see <a href="/books/NBK546574/table/mps3.T.molecular_genetic_testing_used_in/?report=objectonly" target="object" rid-ob="figobmps3Tmoleculargenetictestingusedin">Table 1</a>) or deficiency of the respective lysosomal enzyme (see <a href="#mps3.GeneReview_Scope">scope table</a>) has been identified.</p><p><b>Molecular genetic testing</b> approaches can include a combination of <b>gene-targeted testing</b> (multigene panel) and <b>comprehensive</b>
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<b>genomic testing</b> (exome sequencing, exome array, genome sequencing) depending on the presenting phenotype.</p><p>Gene-targeted testing requires that the clinician determine which gene(s) are likely involved, whereas genomic testing does not. Because the phenotype of MPS III is broad and age dependent, individuals with the distinctive findings described in <a href="#mps3.Suggestive_Findings">Suggestive Findings</a> are likely to be diagnosed using gene-targeted testing (see <a href="#mps3.Option_1">Option 1</a>), whereas:</p><ul><li class="half_rhythm"><div>Those with a phenotype indistinguishable from many other inherited disorders with intellectual disability, developmental regression, and/or significant behavioral issues are more likely to be diagnosed using genomic testing (see <a href="#mps3.Option_2">Option 2</a>).</div></li><li class="half_rhythm"><div>Those in whom the diagnosis of MPS III has not been considered are more likely to be diagnosed using genomic testing (see <a href="#mps3.Option_2">Option 2</a>).</div></li></ul><div id="mps3.Option_1"><h4>Option 1</h4><p>When clinical and laboratory findings suggest the diagnosis of MPS III, molecular genetic testing approaches can include use of a <b>multigene panel</b>.</p><p><b>An MPS III or mucopolysaccharidosis</b>
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<b>multigene panel</b> that includes <i>GNS</i>, <i>HGSNAT</i>, <i>NAGLU</i>, <i>SGSH</i>, and other genes of interest (see <a href="#mps3.Differential_Diagnosis">Differential Diagnosis</a>) is most likely to identify the genetic cause of the condition at the most reasonable cost while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene 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>. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, 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/NBK546574/table/mps3.T.molecular_genetic_testing_used_in/?report=objectonly" target="object" rid-ob="figobmps3Tmoleculargenetictestingusedin">Table 1</a>).</p><p>For an introduction to multigene panels click <a href="/books/n/gene/app5/?report=reader#app5.Multigene_Panels">here</a>. More detailed information for clinicians ordering genetic tests can be found <a href="/books/n/gene/app5/?report=reader#app5.Multigene_Panels_FAQs">here</a>.</p></div><div id="mps3.Option_2"><h4>Option 2</h4><p><b>Comprehensive</b>
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<b>genomic testing</b> does not require the clinician to determine which gene(s) are likely involved. <b>Exome sequencing</b> is most commonly used; <b>genome sequencing</b> is also possible.</p><p>If exome sequencing is not diagnostic, <b>exome array</b> (when clinically available) may be considered to detect (multi)exon deletions or duplications that cannot be detected by sequence analysis.</p><p>For an introduction to comprehensive genomic testing click <a href="/books/n/gene/app5/?report=reader#app5.Comprehensive_Genomic_Testing">here</a>. More detailed information for clinicians ordering genomic testing can be found <a href="/books/n/gene/app5/?report=reader#app5.Comprehensive_Genomic_Testing_1">here</a>.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figmps3Tmoleculargenetictestingusedin"><a href="/books/NBK546574/table/mps3.T.molecular_genetic_testing_used_in/?report=objectonly" target="object" title="Table 1. " class="img_link icnblk_img" rid-ob="figobmps3Tmoleculargenetictestingusedin"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="mps3.T.molecular_genetic_testing_used_in"><a href="/books/NBK546574/table/mps3.T.molecular_genetic_testing_used_in/?report=objectonly" target="object" rid-ob="figobmps3Tmoleculargenetictestingusedin">Table 1. </a></h4><p class="float-caption no_bottom_margin">Molecular Genetic Testing Used in Mucopolysaccharidosis Type III </p></div></div><p><b>Enzymatic activity</b> of the four enzymes produced by <i>GNS</i>, <i>HGSNAT</i>, <i>NAGLU</i>, and <i>SGSH</i> (see <a href="#mps3.GeneReview_Scope">scope table</a>) can be measured in multiple tissues; specifically, peripheral blood leukocytes and cultured skin fibroblasts. Blood plasma can also be used to assay activity of alpha-N-acetylglucosaminidase for diagnosis of MPS IIIB.</p><ul><li class="half_rhythm"><div>The recommended strategy for enzymatic assay is simultaneous enzyme panel testing of all four enzymatic deficiencies associated with MPS IIIA (N-sulphoglucosamine sulphohydrolase), MPS IIIB (alpha-N-acetylglucosaminidase), MPS IIIC (heparan-alpha-glucosaminide N-acetyltransferase), and MPS IIID (N-acetylglucosamine-6-sulfatase). (Note: For alternate enzyme naming systems used by some laboratories, see <a href="#mps3.Nomenclature">Nomenclature</a>.) Deficient or very little enzyme activity in any one of these enzymes along with normal activity of the other three enzymes and clinical signs of the disorder is consistent with diagnosis of the corresponding subtype of MPS III.</div></li><li class="half_rhythm"><div>Deficiency of both enzymes associated with MPS IIIA and MPS IIID (N-sulphoglucosamine sulphohydrolase and N-acetylglucosamine-6-sulfatase, respectively) – in the context of normal activity of the enzymes associated with MPS IIIB and MPS IIIC – may suggest a diagnosis of <a href="/books/n/gene/m-sulfatase-def/?report=reader">multiple sulfatase deficiency</a> rather than MPS III.</div></li><li class="half_rhythm"><div>In fluorometric assays for MPS IIIC, endogenous beta-hexosaminidase is used to convert the intermediate substance into the fluorescence-releasing final product. Therefore, individuals with beta-hexosaminidase deficiencies could receive false positive results for MPS IIIC.</div></li></ul></div></div></div><div id="mps3.Clinical_Characteristics"><h2 id="_mps3_Clinical_Characteristics_">Clinical Characteristics</h2><div id="mps3.Clinical_Description"><h3>Clinical Description</h3><p>Mucopolysaccharidosis type III (MPS III), a multisystem lysosomal storage disease that results from glycosaminoglycan (GAG) accumulation, is characterized by extreme clinical variability. Progressive central nervous system degeneration resulting in severe intellectual disability and developmental regression is the most prominent manifestation. Although often present, the somatic findings characteristic of other mucopolysaccharidoses (MPSs) are generally less clinically striking in individuals with MPS III.</p><p>Despite the universal neurologic decline in affected individuals, clinical severity varies within and among the four MPS III subtypes and even among members of the same family. Individuals with MPS III may have rapidly or slowly progressing disease [<a class="bibr" href="#mps3.REF.valstar.2010c.876" rid="mps3.REF.valstar.2010c.876">Valstar et al 2010c</a>]. Some individuals with an extremely attenuated disease course present in mid-to-late adulthood with early-onset dementia with or without history of intellectual disability [<a class="bibr" href="#mps3.REF.bergerplantinga.2004.479" rid="mps3.REF.bergerplantinga.2004.479">Berger-Plantinga et al 2004</a>, <a class="bibr" href="#mps3.REF.verhoeven.2010.162" rid="mps3.REF.verhoeven.2010.162">Verhoeven et al 2010</a>].</p><p>Life span of individuals with MPS III is unpredictable, but shortened. Death usually occurs in the second or third decade of life secondary to neurologic disease or respiratory tract infections [<a class="bibr" href="#mps3.REF.valstar.2010a.e1348" rid="mps3.REF.valstar.2010a.e1348">Valstar et al 2010a</a>, <a class="bibr" href="#mps3.REF.lavery.2017.168" rid="mps3.REF.lavery.2017.168">Lavery et al 2017</a>]. Although some individuals with more slowly progressive, later-onset, or mild disease can live into their 30s, 40s, or even 50s with excellent medical care, this is atypical. In very rare instances, adults with MPS III have survived into their 60s [<a class="bibr" href="#mps3.REF.verhoeven.2010.162" rid="mps3.REF.verhoeven.2010.162">Verhoeven et al 2010</a>].</p><p>In the following descriptions of clinical involvement in MPS III, it is important to note the potential for bias in the medical literature toward ascertaining/reporting clinical data regarding individuals with the most severe and rapidly progressive disease course.</p><p><b>Craniofacial and physical appearance.</b> Many children have dolichocephaly or macrocephaly. Coarse facies, present in most affected individuals, tend to become more evident over time as GAGs accumulate in soft tissues. Dysmorphisms can include thick alae nasi, lips, and ear helices or lobules and macroglossia. Coarse and thick hair are frequently observed, as are synophrys and hirsutism. Skin is often tough and thick, sometimes causing difficulty with venipuncture.</p><p><b>Hepatosplenomegaly.</b> Abdominal protuberance due to progressive organomegaly can be observed but is not universal. GAG accumulation that results in hepatomegaly and splenomegaly does not lead to dysfunction despite increases in size.</p><p><b>Neurologic.</b> Ventriculomegaly is hypothesized to occur secondary to cerebral atrophy and impaired reabsorption of cerebrospinal fluid. Some individuals may experience symptomatic hydrocephalus.</p><p>Seizure disorders, common during later disease stages, are not universal.</p><p>Progressive neurodegeneration can result in gait disorders, hyperactive reflexes, or spasticity.</p><p><b>Development and cognition.</b> Early childhood development may be normal; however, it is not uncommon for language or other developmental delays to be present from as early as age one year. Developmental delays are frequently evident in affected children by age two to six years; language development is often more delayed than motor development.</p><p>After development plateaus, a progressive loss of motor and cognitive skills begins. In rapidly progressing MPS III, regression may start as early as age three to four years. In those with very mild disease, regression may not become apparent until much later [<a class="bibr" href="#mps3.REF.shapiro.2016" rid="mps3.REF.shapiro.2016">Shapiro et al 2016</a>, <a class="bibr" href="#mps3.REF.whitley.2018.198" rid="mps3.REF.whitley.2018.198">Whitley et al 2018</a>]. If language was acquired, verbal skills are often lost by ages ten to 15 years. Although loss of independent ambulation in most affected individuals occurs between the teen years and the third decade, it can be earlier in those with a more severe disease course. Eventually, neurodegeneration leads to dysphagia, immobility, and unresponsiveness [<a class="bibr" href="#mps3.REF.ruijter.2008.104" rid="mps3.REF.ruijter.2008.104">Ruijter et al 2008</a>].</p><p><b>Psychiatric and behavioral.</b> The behavioral phenotype of MPS III, often a hallmark of the disease, usually begins between ages three and five years. Almost all affected children exhibit hyperactivity often unresponsive to medication. Aggressive and destructive behaviors such as outbursts and tantrums are common and can be difficult to control, particularly in individuals with normal mobility and strength. Behavior becomes less problematic with age due to decreased mobility and initiative resulting from progressive neurodegeneration.</p><p>Klüver-Bucy syndrome (a distinct set of neurobehavioral manifestations with psychic blindness, hypersexuality, disinhibition, hyperorality, and hypermetamorphosis) has been reported in individuals with MPS III [<a class="bibr" href="#mps3.REF.potegal.2013.608" rid="mps3.REF.potegal.2013.608">Potegal et al 2013</a>, <a class="bibr" href="#mps3.REF.hu.2017.253" rid="mps3.REF.hu.2017.253">Hu et al 2017</a>].</p><p>Early-onset dementia is observed in some individuals, particularly those with later-onset or more slowly progressing disease.</p><p>Sleep disturbances, present in 80%-95% of individuals, include difficulties with settling and frequent waking. These sleep disorders are thought to result from irregular sleep/wake patterns; some affected individuals demonstrate complete circadian rhythm reversal [<a class="bibr" href="#mps3.REF.cross.2013.189" rid="mps3.REF.cross.2013.189">Cross & Hare 2013</a>].</p><p><b>Musculoskeletal.</b> Stature of children is often normal or just below normal.</p><p>Joint stiffness or contractures and features of dysostosis multiplex are common, although much less severe than in other MPS disorders. Skeletal manifestations are usually not clinically obvious until after the onset of developmental regression and behavioral concerns.</p><p>Scoliosis and hip dysplasia, two of the more common skeletal findings, are usually not severe enough to require surgical correction. Femoral head osteonecrosis is a common cause of hip pain.</p><p>Carpal tunnel syndrome and trigger digits can occur [<a class="bibr" href="#mps3.REF.white.2011.594" rid="mps3.REF.white.2011.594">White et al 2011</a>].</p><p>Low bone mass and vitamin D insufficiency or deficiency are prevalent and can be observed as early as the teenage years. Patients with decreased mobility or a history of anti-seizure medication use are especially at risk for osteoporosis and fractures [<a class="bibr" href="#mps3.REF.nur.2017.338" rid="mps3.REF.nur.2017.338">Nur et al 2017</a>].</p><p><b>Hearing loss</b> is common and can be conductive, sensorineural, or mixed due to a combination of dysostosis of the ossicles of the middle ear, inner ear abnormalities, and frequent otitis media.</p><p><b>ENT (otolaryngologic).</b> Chronic and recurrent otitis media and rhinitis accompanied by poor sinus drainage are common as are frequent infections of the adenoids and tonsils, which may be enlarged.</p><p><b>Respiratory.</b> Respiratory tract and sinopulmonary infections are common. Abnormal respiration can also be secondary to neurodegeneration, thick secretions with inefficient drainage, and anatomic airway obstruction. Rarely, the adenoids or tonsils are so enlarged that they cause obstructive sleep apnea. However, sleep apnea may also be due to the significant CNS involvement.</p><p><b>Gastrointestinal.</b> Chronic or recurrent loose stools and/or constipation are common, though the primary cause is unknown. Diarrhea typically is episodic, but can be persistent in some. These concerns may be affected by activity or diet and may be exacerbated by frequent antibiotic treatment of recurrent infections.</p><p>Inguinal and umbilical hernias are common. Inguinal hernias may recur after surgical intervention. Umbilical hernias are not usually treated unless they are large or cause other medical concerns.</p><p>With progression of neurodegeneration, many affected individuals develop dysphagia and/or problems with chewing and swallowing food, increasing risks for aspiration pneumonia and weight loss secondary to poor feeding in later disease stages.</p><p><b>Cardiovascular.</b> Although GAG storage in the mitral valve, aortic valve, myocardium, and/or cardiac conduction system (causing atrioventricular block) is common, most individuals with MPS III do not require cardiac intervention. Left ventricle ejection fraction is normal in children, but slightly impaired in adults [<a class="bibr" href="#mps3.REF.nijmeijer.2019.276" rid="mps3.REF.nijmeijer.2019.276">Nijmeijer et al 2019</a>]. Shortened life span and inactivity of older individuals may explain the paucity of clinical cardiac disease in this population to date.</p><p><b>Ophthalmologic.</b> Corneal opacities, such as corneal clouding, are not usually present in individuals with MPS III. Nonetheless, individuals with MPS III can have atrophy of the optic nerve and retinal degeneration (manifesting as pigmentary retinopathy, poor peripheral vision, and night blindness), particularly in late stages of the disease.</p></div><div id="mps3.Phenotype_Correlations_by_Gene"><h3>Phenotype Correlations by Gene</h3><p>The <a href="#mps3.GeneReview_Scope">subtypes of MPS III</a>, caused by biallelic pathogenic variants in <i>SGSH</i> (MPS IIIA), <i>NAGLU</i> (MPS IIIB), <i>HGSNAT</i> (MPS IIIC), or <i>GNS</i> (MPS IIID), are mainly distinguished by their associated enzymatic deficiencies rather than clear phenotypic differences. While each MPS III subtype exhibits variable expressivity, individuals with MPS IIIA typically have the most severe and rapidly progressing disease course [<a class="bibr" href="#mps3.REF.valstar.2010c.876" rid="mps3.REF.valstar.2010c.876">Valstar et al 2010c</a>].</p></div><div id="mps3.GenotypePhenotype_Correlations"><h3>Genotype-Phenotype Correlations</h3><p>No genotype-phenotype correlations for pathogenic variants in <i>GNS</i> and <i>HGSNAT</i> have been identified. <a href="/books/NBK546574/table/mps3.T.genotypephenotype_correlations_in/?report=objectonly" target="object" rid-ob="figobmps3Tgenotypephenotypecorrelationsin">Table 2</a> summarizes genotype-phenotype correlations for <i>NAGLU</i> and <i>SGSH</i>.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figmps3Tgenotypephenotypecorrelationsin"><a href="/books/NBK546574/table/mps3.T.genotypephenotype_correlations_in/?report=objectonly" target="object" title="Table 2. " class="img_link icnblk_img" rid-ob="figobmps3Tgenotypephenotypecorrelationsin"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="mps3.T.genotypephenotype_correlations_in"><a href="/books/NBK546574/table/mps3.T.genotypephenotype_correlations_in/?report=objectonly" target="object" rid-ob="figobmps3Tgenotypephenotypecorrelationsin">Table 2. </a></h4><p class="float-caption no_bottom_margin">Genotype-Phenotype Correlations in Mucopolysaccharidosis Type III </p></div></div></div><div id="mps3.Nomenclature"><h3>Nomenclature</h3><p>The four lysosomal enzymes associated with MPS III may be referred to by an alternate naming system (see <a href="/books/NBK546574/table/mps3.T.alternate_naming_system_for_mps_i/?report=objectonly" target="object" rid-ob="figobmps3Talternatenamingsystemformpsi">Table 3</a>).</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figmps3Talternatenamingsystemformpsi"><a href="/books/NBK546574/table/mps3.T.alternate_naming_system_for_mps_i/?report=objectonly" target="object" title="Table 3. " class="img_link icnblk_img" rid-ob="figobmps3Talternatenamingsystemformpsi"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="mps3.T.alternate_naming_system_for_mps_i"><a href="/books/NBK546574/table/mps3.T.alternate_naming_system_for_mps_i/?report=objectonly" target="object" rid-ob="figobmps3Talternatenamingsystemformpsi">Table 3. </a></h4><p class="float-caption no_bottom_margin">Alternate Naming System for MPS III-Related Enzymes </p></div></div></div><div id="mps3.Prevalence"><h3>Prevalence</h3><p>The combined estimated prevalence of MPS III is between 1:50,000 and 1:250,000 depending on the population studied [<a class="bibr" href="#mps3.REF.khan.2017.227" rid="mps3.REF.khan.2017.227">Khan et al 2017</a>]. This may be an underestimate due to variable expressivity and often mild somatic features of the disease.</p><p>Subtypes MPS IIIA and MPS IIIB are the most commonly observed, with estimated incidences of 1:100,000 and 1:200,000, respectively [<a class="bibr" href="#mps3.REF.zelei.2018.53" rid="mps3.REF.zelei.2018.53">Zelei et al 2018</a>]. MPS IIIC and MPS IIID are, overall, much less common, with estimated incidences of 1:1,500,000 and 1:1,000,000, respectively [<a class="bibr" href="#mps3.REF.andrade.2015.331" rid="mps3.REF.andrade.2015.331">Andrade et al 2015</a>].</p><p>Of note, some subtypes of MPS III are more common in certain geographic regions:</p><ul><li class="half_rhythm"><div>MPS IIIA is globally the most common form of MPS III and the most common type observed in many northern and eastern European nations. It is particularly common in the Cayman Islands, with an incidence estimated as high as 1:400 births, secondary to 1/10 carrier frequency of <a href="/books/NBK546574/table/mps3.T.notable_pathogenic_variants_in_ge/?report=objectonly" target="object" rid-ob="figobmps3Tnotablepathogenicvariantsinge">c.734G>A</a> in <i>SGSH</i> [<a class="bibr" href="#mps3.REF.rady.2002.211" rid="mps3.REF.rady.2002.211">Rady et al 2002</a>].</div></li><li class="half_rhythm"><div>MPS IIIB is more common in southern European populations.</div></li><li class="half_rhythm"><div>MPS IIID has a higher-than-usual prevalence in Italian and Turkish populations [<a class="bibr" href="#mps3.REF.valstar.2010a.e1348" rid="mps3.REF.valstar.2010a.e1348">Valstar et al 2010a</a>].</div></li></ul></div></div><div id="mps3.Genetically_Related_Allelic_Disorde"><h2 id="_mps3_Genetically_Related_Allelic_Disorde_">Genetically Related (Allelic) Disorders</h2><p>Germline pathogenic variants in <i>HGSNAT</i> are also known to be associated with nonsyndromic retinitis pigmentosa (OMIM <a href="https://omim.org/entry/616544" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">616544</a>).</p><p>No phenotypes other than those discussed in this <i>GeneReview</i> are known to be associated with germline pathogenic variants in <i>GNS</i>, <i>NAGLU</i>, or <i>SGSH</i>.</p></div><div id="mps3.Differential_Diagnosis"><h2 id="_mps3_Differential_Diagnosis_">Differential Diagnosis</h2><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figmps3Tgenesofinterestinthedifferen"><a href="/books/NBK546574/table/mps3.T.genes_of_interest_in_the_differen/?report=objectonly" target="object" title="Table 4. " class="img_link icnblk_img" rid-ob="figobmps3Tgenesofinterestinthedifferen"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="mps3.T.genes_of_interest_in_the_differen"><a href="/books/NBK546574/table/mps3.T.genes_of_interest_in_the_differen/?report=objectonly" target="object" rid-ob="figobmps3Tgenesofinterestinthedifferen">Table 4. </a></h4><p class="float-caption no_bottom_margin">Genes of Interest in the Differential Diagnosis of Mucopolysaccharidosis Type III </p></div></div><p><b>Other lysosomal storage diseases (LSDs).</b> Many findings in individuals with MPS III overlap those identified in individuals with other LSDs, particularly other mucopolysaccharide diseases including MPS I and MPS II (see <a href="/books/NBK546574/table/mps3.T.genotypephenotype_correlations_in/?report=objectonly" target="object" rid-ob="figobmps3Tgenotypephenotypecorrelationsin">Table 2</a>). Clinical presentation, biochemical testing, and molecular testing can assist in distinguishing other LSDs with findings that overlap with those typically observed in MPS III.</p><p><b>Autism spectrum disorder.</b> Language delay and behavioral concerns can be the most prominent and earliest clinical features of MPS III. Many children with MPS III are suspected of having autism spectrum disorder prior to correct diagnosis.</p><p><b>Attention-deficit/hyperactivity disorder (ADHD).</b> Children with MPS III who have hyperactivity as their most prominent initial clinical feature may be misdiagnosed as having ADHD as their primary diagnosis.</p></div><div id="mps3.Management"><h2 id="_mps3_Management_">Management</h2><div id="mps3.Evaluations_Following_Initial_Diagn"><h3>Evaluations Following Initial Diagnosis</h3><p>To establish the extent of disease and needs in an individual diagnosed with mucopolysaccharidosis type III (MPS III), the evaluations summarized in <a href="/books/NBK546574/table/mps3.T.recommended_evaluations_following/?report=objectonly" target="object" rid-ob="figobmps3Trecommendedevaluationsfollowing">Table 5</a> (if not performed as part of the evaluation that led to the diagnosis) are recommended.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figmps3Trecommendedevaluationsfollowing"><a href="/books/NBK546574/table/mps3.T.recommended_evaluations_following/?report=objectonly" target="object" title="Table 5. " class="img_link icnblk_img" rid-ob="figobmps3Trecommendedevaluationsfollowing"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="mps3.T.recommended_evaluations_following"><a href="/books/NBK546574/table/mps3.T.recommended_evaluations_following/?report=objectonly" target="object" rid-ob="figobmps3Trecommendedevaluationsfollowing">Table 5. </a></h4><p class="float-caption no_bottom_margin">Recommended Evaluations Following Initial Diagnosis in Individuals with Mucopolysaccharidosis Type III </p></div></div></div><div id="mps3.Treatment_of_Manifestations"><h3>Treatment of Manifestations</h3><p>It is important to note that developmental advances made by individuals with MPS III secondary to implementation of therapy may be short-lived as a result of the progressive nature of disease.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figmps3Ttreatmentofmanifestationsinin"><a href="/books/NBK546574/table/mps3.T.treatment_of_manifestations_in_in/?report=objectonly" target="object" title="Table 6. " class="img_link icnblk_img" rid-ob="figobmps3Ttreatmentofmanifestationsinin"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="mps3.T.treatment_of_manifestations_in_in"><a href="/books/NBK546574/table/mps3.T.treatment_of_manifestations_in_in/?report=objectonly" target="object" rid-ob="figobmps3Ttreatmentofmanifestationsinin">Table 6. </a></h4><p class="float-caption no_bottom_margin">Treatment of Manifestations in Individuals with Mucopolysaccharidosis Type III </p></div></div><div id="mps3.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. In the US, early intervention is a federally funded program available in all states.</p><p><b>Ages 3-5 years.</b> In the US, developmental preschool through the local public school district is recommended. Before placement, an evaluation is made to determine needed services and therapies and an individualized education plan (IEP) is developed.</p><p><b>All ages.</b> Consultation with a developmental pediatrician is recommended to ensure the involvement of appropriate community, state, and educational agencies (US) and to support parents in maximizing quality of life. Some issues to consider:</p><ul><li class="half_rhythm"><div>Individualized education plan (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 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="mps3.Motor_Dysfunction"><h4>Motor Dysfunction</h4><p>
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<b>Gross motor dysfunction</b>
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</p><ul><li class="half_rhythm"><div>Physical therapy is recommended to maximize mobility.</div></li><li class="half_rhythm"><div>Consider use of durable medical equipment as needed (e.g., wheelchairs, walkers, bath chairs, orthotics, adaptive strollers).</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 id="mps3.SocialBehavioral_Concerns"><h4>Social/Behavioral Concerns</h4><p>Children may qualify for and benefit from interventions used in treatment of autism spectrum disorder, including applied behavior analysis (ABA). ABA therapy is targeted to the individual child's behavioral, social, and adaptive strengths and weaknesses and typically performed one on one with a board-certified behavior analyst.</p><p>Consultation with a developmental pediatrician may be helpful in guiding parents through appropriate behavior management strategies or providing prescription medications, such as medication used to treat attention-deficit/hyperactivity disorder, when necessary.</p><p>Concerns about serious aggressive or destructive behavior can be addressed by a pediatric psychiatrist.</p></div><div id="mps3.Palliative_Care"><h4>Palliative Care</h4><p>As MPS III is a neurodegenerative, progressive, and life-limiting illness, resources for palliative care that are available to help reduce suffering from disease manifestations or improve quality of life should be considered and discussed with family members. Specific support resources desired by families will vary, but options for palliative care include respite care, assistance with symptom management, psychological and other forms of support, assistance with medical decision making, and assistance with creating and updating a care plan.</p></div></div><div id="mps3.Surveillance"><h3>Surveillance</h3><p>Due to the progression of MPS III manifestations over time, improvements in symptoms resulting from proper management are not typically long lasting. Consequently, monitoring for deterioration in the affected individual is an appropriate and important part of surveillance.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figmps3Trecommendedsurveillanceforindi"><a href="/books/NBK546574/table/mps3.T.recommended_surveillance_for_indi/?report=objectonly" target="object" title="Table 7. " class="img_link icnblk_img" rid-ob="figobmps3Trecommendedsurveillanceforindi"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="mps3.T.recommended_surveillance_for_indi"><a href="/books/NBK546574/table/mps3.T.recommended_surveillance_for_indi/?report=objectonly" target="object" rid-ob="figobmps3Trecommendedsurveillanceforindi">Table 7. </a></h4><p class="float-caption no_bottom_margin">Recommended Surveillance for Individuals with Mucopolysaccharidosis Type III </p></div></div></div><div id="mps3.AgentsCircumstances_to_Avoid"><h3>Agents/Circumstances to Avoid</h3><p>Though airway management during procedures with anesthesia is not typically difficult, anesthesia conducted in ill-equipped medical centers or by personnel with limited experience with patients with difficult airways is not recommended [<a class="bibr" href="#mps3.REF.clark.2018.1" rid="mps3.REF.clark.2018.1">Clark et al 2018</a>].</p><p>Hip surgery is not recommended for individuals with MPS III due to the development of osteonecrosis and collapse of the femoral head [<a class="bibr" href="#mps3.REF.white.2011.594" rid="mps3.REF.white.2011.594">White et al 2011</a>].</p><p>To minimize risks posed by unpredictable behavior, children with MPS III should be supervised around or have their environment adapted to avoid the following for their safety:</p><ul><li class="half_rhythm"><div>Sharp or fragile furniture</div></li><li class="half_rhythm"><div>Sharp or fragile toys</div></li><li class="half_rhythm"><div>Large electronics</div></li><li class="half_rhythm"><div>High structures or surfaces that pose risks of falls and other injuries</div></li></ul></div><div id="mps3.Evaluation_of_Relatives_at_Risk"><h3>Evaluation of Relatives at Risk</h3><p>See <a href="#mps3.Related_Genetic_Counseling_Issues">Genetic Counseling</a> for issues related to testing of at-risk relatives for genetic counseling purposes.</p></div><div id="mps3.Pregnancy_Management"><h3>Pregnancy Management</h3><p>Very few individuals with MPS III are known to have reproduced. In one case report a woman with slowly progressive MPS IIIB had an unremarkable pregnancy and a healthy child [<a class="bibr" href="#mps3.REF.verhoeven.2010.162" rid="mps3.REF.verhoeven.2010.162">Verhoeven et al 2010</a>]. Due to the prevalence of valvular disease in MPS III, corresponding evaluation and management is appropriate if a woman with MPS III does achieve pregnancy.</p></div><div id="mps3.Therapies_Under_Investigation"><h3>Therapies Under Investigation</h3><p>Despite ongoing research for a variety of therapeutic options for affected individuals, no treatments are currently clinically available for treatment of primary manifestations of MPS III.</p><p><b>Hematopoietic stem cell transplantation (HSCT) and umbilical cord blood transplantation (UCBT)</b> are not currently considered effective treatment options for MPS III due to the lack of evidence of neurologic benefit.</p><p><b>Enzyme replacement therapy (ERT).</b> Due to the inability of intravenous ERT to permeate the blood-brain barrier sufficiently to prevent neurologic disease progression, intravenous ERT has not been investigated in MPS III as intensively as it has for other lysosomal storage diseases.</p><p>Other methods of ERT administration, such as intrathecal injections, are effective in delivering ERT to normalize substrate storage in the CNS of MPS III animal models [<a class="bibr" href="#mps3.REF.king.2016.409" rid="mps3.REF.king.2016.409">King et al 2016</a>]. A clinical trial currently in progress has demonstrated that intrathecal administration of recombinant human heparan-N-sulfatase, which is well tolerated in individuals with MPS IIIA, results in consistent decrease of heparan sulfate in the CSF [<a class="bibr" href="#mps3.REF.jones.2016.198" rid="mps3.REF.jones.2016.198">Jones et al 2016</a>].</p><p><b>Substrate reduction therapy (SRT)</b> is used successfully to treat other lysosomal storage diseases, such as <a href="/books/n/gene/gaucher/?report=reader">Gaucher disease</a>. Ongoing research suggests SRT as a future therapeutic option for MPS III.</p><p>In vitro studies have shown that siRNA targeting of genes that play a role in synthesis of heparan sulfate leads to decreased heparan sulfate synthesis, decreased GAG storage, and a reversal of the phenotype in fibroblasts of patients with MPS IIIC [<a class="bibr" href="#mps3.REF.canals.2015.13654" rid="mps3.REF.canals.2015.13654">Canals et al 2015</a>].</p><p>Although genistein inhibits heparan sulfate synthesis and decreases accumulation of heparan sulfate in plasma and urine, it does not improve manifestations of MPS III at doses of 5 mg/kg/day or 10 mg/kg/day [<a class="bibr" href="#mps3.REF.de_ruijter.2012.110" rid="mps3.REF.de_ruijter.2012.110">de Ruijter et al 2012</a>]. Future studies regarding genistein use at higher doses may determine whether it has clinical efficacy as a treatment for MPS III.</p><p><b>Chaperone-mediated therapy.</b> The use of pharmacologic chaperones to increase residual lysosomal activity is being explored in MPS III. Certain mutated forms of enzymes implicated in the pathogenesis of MPS III can be rescued by chaperones that restore the natural folding of the enzyme to increase its activity. Chaperones are small enough in size to presumably cross the blood-brain barrier and target the cells with mutant enzyme that are the source of neurologic manifestations of MPS III. It has been proposed that low concentrations of specific chaperone molecules could function as partial enzymatic rescues in MPS IIIB or MPS IIIC.</p><p><b>Gene therapy.</b> Ongoing advances in gene therapy may influence treatment of MPS III.</p><p>The use of a variety of MPS III-related gene-encoding viral vectors in mouse and canine models of MPS IIIA, MPS IIIB, and MPS IIID has increased deficient enzyme activity and decreased GAG storage [<a class="bibr" href="#mps3.REF.scarpa.2017.25" rid="mps3.REF.scarpa.2017.25">Scarpa et al 2017</a>].</p><p>In children with MPS IIIA or MPS IIIB, intracerebral gene therapy has been well tolerated; findings suggest neurocognitive benefits, including moderate improvements in sleep and behavior. The most remarkable results are observed in the youngest patients, suggesting that earlier therapy may be more beneficial [<a class="bibr" href="#mps3.REF.tardieu.2014.506" rid="mps3.REF.tardieu.2014.506">Tardieu et al 2014</a>, <a class="bibr" href="#mps3.REF.tardieu.2017.712" rid="mps3.REF.tardieu.2017.712">Tardieu et al 2017</a>]. Additional trials regarding gene therapy for MPS III are under way.</p><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.</p></div></div><div id="mps3.Genetic_Counseling"><h2 id="_mps3_Genetic_Counseling_">Genetic Counseling</h2><p>
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<i>Genetic counseling is the process of providing individuals and families with
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information on the nature, mode(s) of inheritance, and implications of genetic disorders to help them
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make informed medical and personal decisions. The following section deals with genetic
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risk assessment and the use of family history and genetic testing to clarify genetic
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status for family members; it is not meant to address all personal, cultural, or
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ethical issues that may arise or to substitute for consultation with a genetics
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professional</i>. —ED.</p><div id="mps3.Mode_of_Inheritance"><h3>Mode of Inheritance</h3><p>Mucopolysaccharidosis type III (MPS III) is inherited in an autosomal recessive manner.</p></div><div id="mps3.Risk_to_Family_Members"><h3>Risk to Family Members</h3><p>
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<b>Parents of a proband</b>
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</p><ul><li class="half_rhythm"><div>The parents of an affected child are obligate heterozygotes (i.e., carriers of one <i>GNS</i>, <i>HGSNAT</i>, <i>NAGLU</i>, or <i>SGSH</i> pathogenic variant).</div></li><li class="half_rhythm"><div>Heterozygotes (carriers) are asymptomatic and are not at risk of developing the disorder.</div></li></ul><p>
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<b>Sibs of a proband</b>
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</p><ul><li class="half_rhythm"><div>At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier.</div></li><li class="half_rhythm"><div>Heterozygotes (carriers) are asymptomatic and are not at risk of developing the disorder.</div></li></ul><p><b>Offspring of a proband.</b> Unless an individual with MPS III has children with an affected individual or a carrier, his/her offspring will be obligate heterozygotes (carriers) for a pathogenic variant in an MPS III-related gene.</p><p><b>Other family members.</b> Each sib of the proband's parents is at a 50% risk of being a carrier for a pathogenic variant in an MPS III-related gene.</p></div><div id="mps3.Carrier_Detection"><h3>Carrier Detection</h3><p>Carrier testing for at-risk relatives requires prior identification of the <i>GNS</i>, <i>HGSNAT</i>, <i>NAGLU</i>, or <i>SGSH</i> pathogenic variants in the family.</p></div><div id="mps3.Related_Genetic_Counseling_Issues"><h3>Related Genetic Counseling Issues</h3><p>
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<b>Family planning</b>
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</p><ul><li class="half_rhythm"><div>The optimal time for determination of genetic risk, clarification of carrier status, and discussion of the availability of prenatal/preimplantation genetic testing is before pregnancy.</div></li><li class="half_rhythm"><div>It is appropriate to offer genetic counseling (including discussion of potential risks to offspring and reproductive options) to young adults who are affected, are carriers, or are at risk of being carriers.</div></li></ul></div><div id="mps3.Prenatal_Testing_and_Preimplantatio"><h3>Prenatal Testing and Preimplantation Genetic Testing</h3><p>Once the MPS III-causing pathogenic variants have been identified in an affected family member, prenatal testing for a pregnancy at increased risk and preimplantation genetic testing are possible.</p><p>Differences in perspective may exist among medical professionals and within families regarding the use of prenatal testing. 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="mps3.Resources"><h2 id="_mps3_Resources_">Resources</h2><p>
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<i>GeneReviews staff has selected the following disease-specific and/or umbrella
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support organizations and/or registries for the benefit of individuals with this disorder
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and their families. GeneReviews is not responsible for the information provided by other
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organizations. For information on selection criteria, click <a href="/books/n/gene/app4/?report=reader">here</a>.</i></p>
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<ul><li class="half_rhythm"><div>
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<b>Cure Sanfilippo Foundation</b>
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</div><div><b>Email:</b> Contact@CureSanfilippoFoundation.org</div><div>
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<a href="https://curesanfilippofoundation.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">www.curesanfilippofoundation.org</a>
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</div></li><li class="half_rhythm"><div>
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<b>Sanfilippo Children's Foundation</b>
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</div><div>Australia</div><div><b>Phone:</b> 1800 664 878 </div><div>
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<a href="https://www.sanfilippo.org.au/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">www.sanfilippo.org.au</a>
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</div></li><li class="half_rhythm"><div>
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<b>Team Sanfilippo Foundation</b>
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</div><div><b>Phone:</b> 518-879-6571</div><div>
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<a href="https://teamsanfilippo.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">www.teamsanfilippo.org</a>
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</div></li><li class="half_rhythm"><div>
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<b>Canadian Society for Mucopolysaccharide and Related Diseases</b>
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</div><div>Canada</div><div><b>Phone:</b> 800-667-1846</div><div><b>Email:</b> info@mpssociety.ca</div><div>
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<a href="http://www.mpssociety.ca" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">mpssociety.ca</a>
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</div></li><li class="half_rhythm"><div>
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<b>MPS Society</b>
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</div><div>United Kingdom</div><div><b>Phone:</b> 0345 389 9901</div><div><b>Email:</b> mps@mpssociety.org.uk</div><div>
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<a href="https://www.mpssociety.org.uk/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">mpssociety.org.uk</a>
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</div></li><li class="half_rhythm"><div>
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<b>National MPS Society</b>
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</div><div><b>Phone:</b> 877-MPS-1001</div><div>
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<a href="http://www.mpssociety.org" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">mpssociety.org</a>
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</div></li></ul>
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</div><div id="mps3.Molecular_Genetics"><h2 id="_mps3_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 class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figmps3molgenTA"><a href="/books/NBK546574/table/mps3.molgen.TA/?report=objectonly" target="object" title="Table A." class="img_link icnblk_img" rid-ob="figobmps3molgenTA"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="mps3.molgen.TA"><a href="/books/NBK546574/table/mps3.molgen.TA/?report=objectonly" target="object" rid-ob="figobmps3molgenTA">Table A.</a></h4><p class="float-caption no_bottom_margin">Mucopolysaccharidosis Type III: Genes and Databases </p></div></div><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figmps3molgenTB"><a href="/books/NBK546574/table/mps3.molgen.TB/?report=objectonly" target="object" title="Table B." class="img_link icnblk_img" rid-ob="figobmps3molgenTB"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="mps3.molgen.TB"><a href="/books/NBK546574/table/mps3.molgen.TB/?report=objectonly" target="object" rid-ob="figobmps3molgenTB">Table B.</a></h4><p class="float-caption no_bottom_margin">OMIM Entries for Mucopolysaccharidosis Type III (View All in OMIM) </p></div></div><div id="mps3.Molecular_Pathogenesis"><h3>Molecular Pathogenesis</h3><p><i>GNS</i>, <i>HGSNAT</i>, <i>NAGLU</i>, and <i>SGSH</i> encode four distinct lysosomal enzymes that play separate, yet critical, roles in the heparan sulfate degradation pathway. When one of these four enzymes is deficient, heparan sulfate is not fully catabolized and the accumulation of this glycosaminoglycan (GAG) results.</p><p><b>Mechanism of disease causation.</b> Pathogenic variants in <i>GNS</i>, <i>HGSNAT</i>, <i>NAGLU</i>, and <i>SGSH</i> causing loss of function are the cause of MPS III.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figmps3Tnotablepathogenicvariantsinge"><a href="/books/NBK546574/table/mps3.T.notable_pathogenic_variants_in_ge/?report=objectonly" target="object" title="Table 8. " class="img_link icnblk_img" rid-ob="figobmps3Tnotablepathogenicvariantsinge"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="mps3.T.notable_pathogenic_variants_in_ge"><a href="/books/NBK546574/table/mps3.T.notable_pathogenic_variants_in_ge/?report=objectonly" target="object" rid-ob="figobmps3Tnotablepathogenicvariantsinge">Table 8. </a></h4><p class="float-caption no_bottom_margin">Notable Pathogenic Variants in Genes Causing Mucopolysaccharidosis Type III </p></div></div></div></div><div id="mps3.References"><h2 id="_mps3_References_">References</h2><div id="mps3.Literature_Cited"><h3>Literature Cited</h3><ul class="simple-list"><li class="half_rhythm"><p><div class="bk_ref" id="mps3.REF.andrade.2015.331">Andrade F, Aldámiz-Echevarría L, Llarena M, Couce ML. Sanfilippo syndrome: Overall review. <span><span class="ref-journal">Pediatr Int. </span>2015;<span class="ref-vol">57</span>:331–8.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/25851924" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25851924</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="mps3.REF.bergerplantinga.2004.479">Berger-Plantinga EG, Vanneste JA, Groener JE, van Schooneveld MJ. Adult-onset dementia and retinitis pigmentosa due to mucopolysaccharidosis III-C in two sisters. <span><span class="ref-journal">J Neurol. </span>2004;<span class="ref-vol">251</span>:479–81.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/15083297" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15083297</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="mps3.REF.canals.2015.13654">Canals I, Benetó N, Cozar M, Vilageliu L, Grinberg D. EXTL2 and EXTL3 inhibition with siRNAs as a promising substrate reduction therapy for Sanfilippo C syndrome. <span><span class="ref-journal">Sci Rep. </span>2015;<span class="ref-vol">5</span>:13654.</span> [<a href="/pmc/articles/PMC4561882/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4561882</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/26347037" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26347037</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="mps3.REF.champion.2010.51">Champion KJ, Basehore MJ, Wood T, Destrée A, Vannuffel P, Maystadt I. Identification and characterization of a novel homozygous deletion in the alpha-N-acetylglucosaminidase gene in a patient with Sanfilippo type B syndrome (mucopolysaccharidosis IIIB). <span><span class="ref-journal">Mol Genet Metab. </span>2010;<span class="ref-vol">100</span>:51–6.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/20138557" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20138557</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="mps3.REF.clark.2018.1">Clark BM, Sprung J, Weingarten TN, Warner ME. Anesthesia for patients with mucopolysaccharidoses: Comprehensive review of the literature with emphasis on airway management. <span><span class="ref-journal">Bosn J Basic Med Sci. </span>2018;<span class="ref-vol">18</span>:1–7.</span> [<a href="/pmc/articles/PMC5826667/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5826667</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/28590232" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28590232</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="mps3.REF.cross.2013.189">Cross EM, Hare DJ. Behavioural phenotypes of the mucopolysaccharide disorders: a systematic literature review of cognitive, motor, social, linguistic and behavioural presentation in the MPS disorders. <span><span class="ref-journal">J Inherit Metab Dis. </span>2013;<span class="ref-vol">36</span>:189–200.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/23385295" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23385295</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="mps3.REF.de_ruijter.2012.110">de Ruijter J, Valstar MJ, Narajczyk M, Wegrzyn G, Kulik W, Ijlst L, Wagemans T, van der Wal WM, Wijburg FA. Genistein in Sanfilippo disease: a randomized controlled crossover trial. <span><span class="ref-journal">Ann Neurol. </span>2012;<span class="ref-vol">71</span>:110–20.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/22275257" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22275257</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="mps3.REF.hu.2017.253">Hu H, Hübner C, Lukacs Z, Musante L, Gill E, Wienker TF, Ropers HH, Knierim E, Schuelke M. Klüver-Bucy syndrome associated with a recessive variant in HGSNAT in two siblings with Mucopolysaccharidosis type IIIC (Sanfilippo C). <span><span class="ref-journal">Eur J Hum Genet. </span>2017;<span class="ref-vol">25</span>:253–6.</span> [<a href="/pmc/articles/PMC5255949/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5255949</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/27827379" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27827379</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="mps3.REF.jones.2016.198">Jones SA, Breen C, Heap F, Rust S, de Ruijter J, Tump E, Marchal JP, Pan L, Qiu Y, Chung JK, Nair N, Haslett PA, Barbier AJ, Wijburg FA. A phase 1/2 study of intrathecal heparan-N-sulfatase in patients with mucopolysaccharidosis IIIA. <span><span class="ref-journal">Mol Genet Metab. </span>2016;<span class="ref-vol">118</span>:198–205.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/27211612" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27211612</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="mps3.REF.kalkan_ucar.2010.156">Kalkan Ucar S, Ozbaran B, Demiral N, Yuncu Z, Erermis S, Coker M. Clinical overview of children with mucopolysaccharidosis type IIIA and effect of Risperidone treatment on children and their mothers psychological status. <span><span class="ref-journal">Brain Dev. </span>2010;<span class="ref-vol">32</span>:156–61.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/19217229" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19217229</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="mps3.REF.khan.2017.227">Khan SA, Peracha H, Ballhausen D, Wiesbauer A, Rohrbach M, Gautschi M, Mason RW, Giugliani R, Suzuki Y, Orii KE, Orii T, Tomatsu S. Epidemiology of mucopolysaccharidoses. <span><span class="ref-journal">Mol Genet Metab. </span>2017;<span class="ref-vol">121</span>:227–40.</span> [<a href="/pmc/articles/PMC5653283/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5653283</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/28595941" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28595941</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="mps3.REF.king.2016.409">King B, Hassiotis S, Rozaklis T, Beard H, Trim PJ, Snel MF, Hopwood JJ, Hemsley KM. Low-dose, continuous enzyme replacement therapy ameliorates brain pathology in the neurodegenerative lysosomal disorder mucopolysaccharidosis type IIIA. <span><span class="ref-journal">J Neurochem. </span>2016;<span class="ref-vol">137</span>:409–22.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/26762778" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26762778</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="mps3.REF.lavery.2017.168">Lavery C, Hendriksz CJ, Jones SA. Mortality in patients with Sanfilippo syndrome. <span><span class="ref-journal">Orphanet J Rare Dis. </span>2017;<span class="ref-vol">12</span>:168.</span> [<a href="/pmc/articles/PMC5654004/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5654004</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/29061114" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 29061114</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="mps3.REF.mahon.2014.e84128">Mahon LV, Lomax M, Grant S, Cross E, Hare DJ, Wraith JE, Jones S, Bigger B, Langford-Smith K, Canal M. Assessment of sleep in children with mucopolysaccharidosis type III. <span><span class="ref-journal">PLoS One. </span>2014;<span class="ref-vol">9</span>:e84128. </span> [<a href="/pmc/articles/PMC3913580/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3913580</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/24504123" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24504123</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="mps3.REF.meyer.2008.770">Meyer A, Kossow K, Gal A, Steglich C, Mühlhausen C, Ullrich K, Braulke T, Muschol N. The mutation p.Ser298Pro in the sulphamidase gene (SGSH) is associated with a slowly progressive clinical phenotype in mucopolysaccharidosis type IIIA (Sanfilippo A syndrome). <span><span class="ref-journal">Hum Mutat. </span>2008;<span class="ref-vol">29</span>:770.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/18407553" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18407553</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="mps3.REF.nijmeijer.2019.276">Nijmeijer SCM, de Bruin-Bon RHACM, Wijburg FA, Kuipers IM. Cardiac disease in mucopolysaccharidosis type III. <span><span class="ref-journal">J Inherit Metab Dis. </span>2019;<span class="ref-vol">42</span>:276–85.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/30671988" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 30671988</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="mps3.REF.nur.2017.338">Nur BG, Nur H, Mihci E. Bone mineral density in patients with mucopolysaccharidosis type III. <span><span class="ref-journal">J Bone Miner Metab. </span>2017;<span class="ref-vol">35</span>:338–43.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/27193466" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27193466</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="mps3.REF.potegal.2013.608">Potegal M, Yund B, Rudser K, Ahmed A, Delaney K, Nestrasil I, Whitley CB, Shapiro EG. Mucopolysaccharidosis Type IIIA presents as a variant of Klüver-Bucy syndrome. <span><span class="ref-journal">J Clin Exp Neuropsychol. </span>2013;<span class="ref-vol">35</span>:608–16.</span> [<a href="/pmc/articles/PMC3931576/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3931576</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/23745734" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23745734</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="mps3.REF.rady.2002.211">Rady PL, Surendran S, Vu AT, Hawkins JC, Michals-Matalon K, Tyring SK, Merren J, Kumar AK, Matalon R. Founder mutation R245H of Sanfilippo syndrome type A in the Cayman Islands. <span><span class="ref-journal">Genet Test. </span>2002;<span class="ref-vol">6</span>:211–5.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/12490062" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12490062</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="mps3.REF.ruijter.2008.104">Ruijter GJ, Valstar MJ, van de Kamp JM, van der Helm RM, Durand S, van Diggelen OP, Wevers RA, Poorthuis BJ, Pshezhetsky AV, Wijburg FA. Clinical and genetic spectrum of Sanfilippo type C (MPS IIIC) disease in The Netherlands. <span><span class="ref-journal">Mol Genet Metab. </span>2008;<span class="ref-vol">93</span>:104–11.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/18024218" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18024218</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="mps3.REF.scarpa.2017.25">Scarpa M, Orchard PJ, Schulz A, Dickson PI, Haskins ME, Escolar ML, Giugliani R. Treatment of brain disease in the mucopolysaccharidoses. <span><span class="ref-journal">Mol Genet Metab. </span>2017;<span class="ref-vol">122S</span>:25–34.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/29153844" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 29153844</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="mps3.REF.shapiro.2016">Shapiro EG, Nestrasil I, Delaney KA, Rudser K, Kovac V, Nair N, Richard CW, Haslett P, Whitley CB. A prospective natural history study of mucopolysaccharidosis type IIIA. J Pediatr. 2016;170:278-87.e1-4. [<a href="/pmc/articles/PMC4769976/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4769976</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/26787381" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26787381</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="mps3.REF.tardieu.2014.506">Tardieu M, Zérah M, Husson B, de Bournonville S, Deiva K, Adamsbaum C, Vincent F, Hocquemiller M, Broissand C, Furlan V, Ballabio A, Fraldi A, Crystal RG, Baugnon T, Roujeau T, Heard JM, Danos O. Intracerebral administration of adeno-associated viral vector serotype rh.10 carrying human SGSH and SUMF1 cDNAs in children with mucopolysaccharidosis type IIIA disease: results of a phase I/II trial. <span><span class="ref-journal">Hum Gene Ther. </span>2014;<span class="ref-vol">25</span>:506–16.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/24524415" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24524415</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="mps3.REF.tardieu.2017.712">Tardieu M, Zérah M, Gougeon ML, Ausseil J, de Bournonville S, Husson B, Zafeiriou D, Parenti G, Bourget P, Poirier B, Furlan V, Artaud C, Baugnon T, Roujeau T, Crystal RG, Meyer C, Deiva K, Heard JM. Intracerebral gene therapy in children with mucopolysaccharidosis type IIIB syndrome: an uncontrolled phase 1/2 clinical trial. <span><span class="ref-journal">Lancet Neurol. </span>2017;<span class="ref-vol">16</span>:712–20.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/28713035" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28713035</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="mps3.REF.valstar.2010a.e1348">Valstar MJ, Bertoli-Avella AM, Wessels MW, Ruijter GJ, de Graaf B, Olmer R, Elfferich P, Neijs S, Kariminejad R, Suheyl Ezgü F, Tokatli A, Czartoryska B, Bosschaart AN, van den Bos-Terpstra F, Puissant H, Bürger F, Omran H, Eckert D, Filocamo M, Simeonov E, Willems PJ, Wevers RA, Niermeijer MF, Halley DJ, Poorthuis BJ, van Diggelen OP. Mucopolysaccharidosis type IIID: 12 new patients and 15 novel mutations. <span><span class="ref-journal">Hum Mutat. </span>2010a;<span class="ref-vol">31</span>:E1348–60.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/20232353" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20232353</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="mps3.REF.valstar.2010b.759">Valstar MJ, Bruggenwirth HT, Olmer R, Wevers RA, Verheijen FW, Poorthuis BJ, Halley DJ, Wijburg FA. Mucopolysaccharidosis type IIIB may predominantly present with an attenuated clinical phenotype. <span><span class="ref-journal">J Inherit Metab Dis. </span>2010b;<span class="ref-vol">33</span>:759–67.</span> [<a href="/pmc/articles/PMC2992652/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC2992652</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/20852935" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20852935</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="mps3.REF.valstar.2010c.876">Valstar MJ, Neijs S, Bruggenwirth HT, Olmer R, Ruijter GJ, Wevers RA, van Diggelen OP, Poorthuis BJ, Halley DJ, Wijburg FA. Mucopolysaccharidosis type IIIA: clinical spectrum and genotype-phenotype correlations. <span><span class="ref-journal">Ann Neurol. </span>2010c;<span class="ref-vol">68</span>:876–87.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/21061399" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21061399</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="mps3.REF.verhoeven.2010.162">Verhoeven WM, Csepán R, Marcelis CL, Lefeber DJ, Egger JI, Tuinier S. Sanfilippo B in an elderly female psychiatric patient: a rare but relevant diagnosis in presenile dementia. <span><span class="ref-journal">Acta Psychiatr Scand. </span>2010;<span class="ref-vol">122</span>:162–5.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/20040070" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20040070</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="mps3.REF.weber.1999.34">Weber B, Guo XH, Kleijer WJ, van de Kamp JJ, Poorthuis BJ, Hopwood JJ. Sanfilippo type B syndrome (mucopolysaccharidosis III B): allelic heterogeneity corresponds to the wide spectrum of clinical phenotypes. <span><span class="ref-journal">Eur J Hum Genet. </span>1999;<span class="ref-vol">7</span>:34–44.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/10094189" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10094189</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="mps3.REF.white.2011.594">White KK, Karol LA, White DR, Hale S. Musculoskeletal manifestations of Sanfilippo Syndrome (mucopolysaccharidosis type III). <span><span class="ref-journal">J Pediatr Orthop. </span>2011;<span class="ref-vol">31</span>:594–8.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/21654471" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21654471</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="mps3.REF.whitley.2018.198">Whitley CB, Cleary M, Mengel KE, Harmatz P, Shapiro E, Nestrasil I, Haslett P, Whiteman D, Alexanderian D. Observational prospective natural history of patients with Sanfilippo syndrome type B. <span><span class="ref-journal">J Pediatr. </span>2018;<span class="ref-vol">197</span>:198–206.e2.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/29661560" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 29661560</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="mps3.REF.zhao.1998.53">Zhao HG, Aronovich EL, Whitley CB. Genotype-phenotype correspondence in Sanfilippo syndrome type B. <span><span class="ref-journal">Am J Hum Genet. </span>1998;<span class="ref-vol">62</span>:53–63.</span> [<a href="/pmc/articles/PMC1376807/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC1376807</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/9443875" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9443875</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="mps3.REF.zelei.2018.53">Zelei T, Csetneki K, Vokó Z, Siffel C. Epidemiology of Sanfilippo syndrome: results of a systematic literature review. <span><span class="ref-journal">Orphanet J Rare Dis. </span>2018;<span class="ref-vol">13</span>:53.</span> [<a href="/pmc/articles/PMC5891921/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5891921</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/29631636" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 29631636</span></a>]</div></p></li></ul></div></div><div id="mps3.Chapter_Notes"><h2 id="_mps3_Chapter_Notes_">Chapter Notes</h2><div id="mps3.Author_Notes"><h3>Author Notes</h3><p>Victoria Wagner, MS, CGC, is a genetic counselor at McGovern Medical School at the University of Texas Health Science Center at Houston (UTHealth Houston) and is involved in general and developmental screening genetics clinics. She also has clinical and research interests in the lysosomal storage diseases (LSDs), particularly in the mucopolysaccharidoses (MPSs).</p><p>Hope Northrup, MD, is a geneticist and physician scientist at McGovern Medical School at UTHealth Houston. Her research and clinical interests include tuberous sclerosis complex (TSC) and a variety of inborn errors of metabolism – most notably, phenylketonuria (PKU) and LSDs.</p></div><div id="mps3.Revision_History"><h3>Revision History</h3><ul><li class="half_rhythm"><div>19 September 2019 (bp) Review posted live</div></li><li class="half_rhythm"><div>13 March 2019 (vw) Original submission</div></li></ul></div></div><div id="bk_toc_contnr"></div></div></div><div class="fm-sec"><h2 id="_NBK546574_pubdet_">Publication Details</h2><h3>Author Information and Affiliations</h3><div class="contrib half_rhythm"><span itemprop="author">Victoria F Wagner</span>, MS, CGC<div class="affiliation small">Department of Pediatrics
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Division of Medical Genetics
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McGovern Medical School
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University of Texas Health Science Center at Houston
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Houston, Texas<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="ude.cmt.htu@rengaw.airotciv" class="oemail">ude.cmt.htu@rengaw.airotciv</a></div></div></div><div class="contrib half_rhythm"><span itemprop="author">Hope Northrup</span>, MD<div class="affiliation small">Department of Pediatrics
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Division of Medical Genetics
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McGovern Medical School
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University of Texas Health Science Center at Houston
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Houston, Texas<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="ude.cmt.htu@purhtron.epoh" class="oemail">ude.cmt.htu@purhtron.epoh</a></div></div></div><h3>Publication History</h3><p class="small">Initial Posting: <span itemprop="datePublished">September 19, 2019</span>.</p><h3>Copyright</h3><div><div class="half_rhythm"><a href="/books/about/copyright/">Copyright</a> © 1993-2025, University of Washington, Seattle. GeneReviews is
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a registered trademark of the University of Washington, Seattle. All rights
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reserved.<p class="small">GeneReviews® chapters are owned by the University of Washington. Permission is
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contact: <a href="mailto:dev@null" data-email="ude.wu@tssamda" class="oemail">ude.wu@tssamda</a>.</p></div></div><h3>Publisher</h3><p><a href="http://www.washington.edu" ref="pagearea=page-banner&targetsite=external&targetcat=link&targettype=publisher">University of Washington, Seattle</a>, Seattle (WA)</p><h3>NLM Citation</h3><p>Wagner VF, Northrup H. Mucopolysaccharidosis Type III. 2019 Sep 19. In: Adam MP, Feldman J, Mirzaa GM, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2025. <span class="bk_cite_avail"></span></p></div><div class="small-screen-prev"><a href="/books/n/gene/hunter/?report=reader"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M75,30 c-80,60 -80,0 0,60 c-30,-60 -30,0 0,-60"></path><text x="20" y="28" textLength="60" style="font-size:25px">Prev</text></svg></a></div><div class="small-screen-next"><a href="/books/n/gene/mps4a/?report=reader"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M25,30c80,60 80,0 0,60 c30,-60 30,0 0,-60"></path><text x="20" y="28" textLength="60" style="font-size:25px">Next</text></svg></a></div></article><article data-type="table-wrap" id="figobmps3Td"><div id="mps3.Td" class="table"><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK546574/table/mps3.Td/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__mps3.Td_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_mps3.Td_1_1_1_1" colspan="3" scope="colgroup" rowspan="1" style="text-align:left;vertical-align:middle;">Mucopolysaccharidosis Type III: Included Subtypes</th></tr></thead><tbody><tr><td headers="hd_h_mps3.Td_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Subtype</b>
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</td><td headers="hd_h_mps3.Td_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Gene</b>
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</td><td headers="hd_h_mps3.Td_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Enzyme <sup>1</sup></b>
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</td></tr><tr><td headers="hd_h_mps3.Td_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">MPS IIIA</td><td headers="hd_h_mps3.Td_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>SGSH</i>
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</td><td headers="hd_h_mps3.Td_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">N-sulphoglucosamine sulphohydrolase</td></tr><tr><td headers="hd_h_mps3.Td_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">MPS IIIB</td><td headers="hd_h_mps3.Td_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>NAGLU</i>
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</td><td headers="hd_h_mps3.Td_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Alpha-N-acetylglucosaminidase,</td></tr><tr><td headers="hd_h_mps3.Td_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">MPS IIIC</td><td headers="hd_h_mps3.Td_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>HGSNAT</i>
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</td><td headers="hd_h_mps3.Td_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Heparan-alpha-glucosaminide N-acetyltransferase</td></tr><tr><td headers="hd_h_mps3.Td_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">MPS IIID</td><td headers="hd_h_mps3.Td_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>GNS</i>
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</td><td headers="hd_h_mps3.Td_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">N-acetylglucosamine-6-sulfatase</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">MPS = mucopolysaccharidosis</p></div></dd></dl><dl class="bkr_refwrap"><dt>1. </dt><dd><div id="mps3.TF.d.1"><p class="no_margin">See <a href="#mps3.Nomenclature">Nomenclature</a> for alternate names that may be used to refer to these enzymes.</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobmps3Tmoleculargenetictestingusedin"><div id="mps3.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 Mucopolysaccharidosis Type III</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK546574/table/mps3.T.molecular_genetic_testing_used_in/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__mps3.T.molecular_genetic_testing_used_in_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_mps3.T.molecular_genetic_testing_used_in_1_1_1_1" rowspan="2" scope="col" colspan="1" headers="hd_h_mps3.T.molecular_genetic_testing_used_in_1_1_1_1" style="text-align:left;vertical-align:middle;">Gene <sup>1, 2</sup></th><th id="hd_h_mps3.T.molecular_genetic_testing_used_in_1_1_1_2" rowspan="2" scope="col" colspan="1" headers="hd_h_mps3.T.molecular_genetic_testing_used_in_1_1_1_2" style="text-align:left;vertical-align:middle;">Proportion of MPS III Attributed to Pathogenic Variants in Gene <sup>3</sup></th><th id="hd_h_mps3.T.molecular_genetic_testing_used_in_1_1_1_3" colspan="2" scope="colgroup" rowspan="1" style="text-align:left;vertical-align:middle;">Proportion of Pathogenic Variants <sup>4</sup> Detectable by Method</th></tr><tr><th headers="hd_h_mps3.T.molecular_genetic_testing_used_in_1_1_1_3" id="hd_h_mps3.T.molecular_genetic_testing_used_in_1_1_2_1" colspan="1" scope="colgroup" rowspan="1" style="text-align:left;vertical-align:middle;">Sequence analysis <sup>5</sup></th><th headers="hd_h_mps3.T.molecular_genetic_testing_used_in_1_1_1_3" id="hd_h_mps3.T.molecular_genetic_testing_used_in_1_1_2_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Gene-targeted deletion/duplication analysis <sup>6</sup></th></tr></thead><tbody><tr><td headers="hd_h_mps3.T.molecular_genetic_testing_used_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>GNS</i>
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</td><td headers="hd_h_mps3.T.molecular_genetic_testing_used_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">6%</td><td headers="hd_h_mps3.T.molecular_genetic_testing_used_in_1_1_1_3 hd_h_mps3.T.molecular_genetic_testing_used_in_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">~84% <sup>7</sup></td><td headers="hd_h_mps3.T.molecular_genetic_testing_used_in_1_1_1_3 hd_h_mps3.T.molecular_genetic_testing_used_in_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">~16% <sup>7</sup></td></tr><tr><td headers="hd_h_mps3.T.molecular_genetic_testing_used_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>HGSNAT</i>
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</td><td headers="hd_h_mps3.T.molecular_genetic_testing_used_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">4%</td><td headers="hd_h_mps3.T.molecular_genetic_testing_used_in_1_1_1_3 hd_h_mps3.T.molecular_genetic_testing_used_in_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">~98% <sup>8</sup></td><td headers="hd_h_mps3.T.molecular_genetic_testing_used_in_1_1_1_3 hd_h_mps3.T.molecular_genetic_testing_used_in_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Unknown <sup>9</sup></td></tr><tr><td headers="hd_h_mps3.T.molecular_genetic_testing_used_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>NAGLU</i>
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</td><td headers="hd_h_mps3.T.molecular_genetic_testing_used_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">30%</td><td headers="hd_h_mps3.T.molecular_genetic_testing_used_in_1_1_1_3 hd_h_mps3.T.molecular_genetic_testing_used_in_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">~90% <sup>10</sup></td><td headers="hd_h_mps3.T.molecular_genetic_testing_used_in_1_1_1_3 hd_h_mps3.T.molecular_genetic_testing_used_in_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Unknown <sup>9</sup></td></tr><tr><td headers="hd_h_mps3.T.molecular_genetic_testing_used_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>SGSH</i>
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</td><td headers="hd_h_mps3.T.molecular_genetic_testing_used_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">60%</td><td headers="hd_h_mps3.T.molecular_genetic_testing_used_in_1_1_1_3 hd_h_mps3.T.molecular_genetic_testing_used_in_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">~98% <sup>11</sup></td><td headers="hd_h_mps3.T.molecular_genetic_testing_used_in_1_1_1_3 hd_h_mps3.T.molecular_genetic_testing_used_in_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Unknown <sup>9</sup></td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt>1. </dt><dd><div id="mps3.TF.1.1"><p class="no_margin">Genes are listed in alphabetic order.</p></div></dd></dl><dl class="bkr_refwrap"><dt>2. </dt><dd><div id="mps3.TF.1.2"><p class="no_margin">See <a href="/books/NBK546574/?report=reader#mps3.molgen.TA">Table A. Genes and Databases</a> for chromosome locus and protein.</p></div></dd></dl><dl class="bkr_refwrap"><dt>3. </dt><dd><div id="mps3.TF.1.3"><p class="no_margin">
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<a class="bibr" href="#mps3.REF.andrade.2015.331" rid="mps3.REF.andrade.2015.331">Andrade et al [2015]</a>
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</p></div></dd></dl><dl class="bkr_refwrap"><dt>4. </dt><dd><div id="mps3.TF.1.4"><p class="no_margin">See <a href="#mps3.Molecular_Genetics">Molecular Genetics</a> for information on allelic variants detected in this gene.</p></div></dd></dl><dl class="bkr_refwrap"><dt>5. </dt><dd><div id="mps3.TF.1.5"><p class="no_margin">Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click <a href="/books/n/gene/app2/?report=reader">here</a>.</p></div></dd></dl><dl class="bkr_refwrap"><dt>6. </dt><dd><div id="mps3.TF.1.6"><p class="no_margin">Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications. Gene-targeted deletion/duplication testing will detect deletions ranging from a single exon to the whole gene; however, breakpoints of large deletions and/or deletion of adjacent genes (e.g., those described by <a class="bibr" href="#mps3.REF.champion.2010.51" rid="mps3.REF.champion.2010.51">Champion et al [2010]</a> and <a class="bibr" href="#mps3.REF.valstar.2010a.e1348" rid="mps3.REF.valstar.2010a.e1348">Valstar et al [2010a]</a>) may not be detected by these methods.</p></div></dd></dl><dl class="bkr_refwrap"><dt>7. </dt><dd><div id="mps3.TF.1.7"><p class="no_margin">The detection rate for pathogenic variants in <i>GNS</i> by sequence analysis in 16 individuals with MPS IIID was approximately 84%. The other 16% were exon or large intragenic deletions [<a class="bibr" href="#mps3.REF.valstar.2010a.e1348" rid="mps3.REF.valstar.2010a.e1348">Valstar et al 2010a</a>].</p></div></dd></dl><dl class="bkr_refwrap"><dt>8. </dt><dd><div id="mps3.TF.1.8"><p class="no_margin">The detection rate for pathogenic variants in <i>HGSNAT</i> by sequence analysis in 29 individuals with MPS IIIC was approximately 98% [<a class="bibr" href="#mps3.REF.ruijter.2008.104" rid="mps3.REF.ruijter.2008.104">Ruijter et al 2008</a>].</p></div></dd></dl><dl class="bkr_refwrap"><dt>9. </dt><dd><div id="mps3.TF.1.9"><p class="no_margin">No data on detection rate of gene-targeted deletion/duplication analysis are available.</p></div></dd></dl><dl class="bkr_refwrap"><dt>10. </dt><dd><div id="mps3.TF.1.10"><p class="no_margin">In a study of 24 individuals, the detection rate for pathogenic variants in <i>NAGLU</i> was approximately 90% [<a class="bibr" href="#mps3.REF.valstar.2010b.759" rid="mps3.REF.valstar.2010b.759">Valstar et al 2010b</a>].</p></div></dd></dl><dl class="bkr_refwrap"><dt>11. </dt><dd><div id="mps3.TF.1.11"><p class="no_margin">In DNA analysis of 101 individuals with MPS IIIA, the detection rate for pathogenic variants in <i>SGSH</i> was approximately 98% [<a class="bibr" href="#mps3.REF.valstar.2010c.876" rid="mps3.REF.valstar.2010c.876">Valstar et al 2010c</a>].</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobmps3Tgenotypephenotypecorrelationsin"><div id="mps3.T.genotypephenotype_correlations_in" class="table"><h3><span class="label">Table 2. </span></h3><div class="caption"><p>Genotype-Phenotype Correlations in Mucopolysaccharidosis Type III</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK546574/table/mps3.T.genotypephenotype_correlations_in/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__mps3.T.genotypephenotype_correlations_in_lrgtbl__"><table><thead><tr><th id="hd_h_mps3.T.genotypephenotype_correlations_in_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Gene<br />(MPS<br />Subtype)</th><th id="hd_h_mps3.T.genotypephenotype_correlations_in_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Genotype-Phenotype Correlation</th></tr></thead><tbody><tr><td headers="hd_h_mps3.T.genotypephenotype_correlations_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>NAGLU</i><br />(MPS IIIB)</td><td headers="hd_h_mps3.T.genotypephenotype_correlations_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<ul><li class="half_rhythm"><div>Homozygosity for variants causing premature termination of the protein product (nonsense or frameshift pathogenic variants) results in more severe or rapidly progressing phenotypes [<a class="bibr" href="#mps3.REF.zhao.1998.53" rid="mps3.REF.zhao.1998.53">Zhao et al 1998</a>, <a class="bibr" href="#mps3.REF.weber.1999.34" rid="mps3.REF.weber.1999.34">Weber et al 1999</a>].</div></li><li class="half_rhythm"><div>Homozygosity for nonsense variant <a href="/books/NBK546574/table/mps3.T.notable_pathogenic_variants_in_ge/?report=objectonly" target="object" rid-ob="figobmps3Tnotablepathogenicvariantsinge">p.Arg297Ter</a> or missense variants <a href="/books/NBK546574/table/mps3.T.notable_pathogenic_variants_in_ge/?report=objectonly" target="object" rid-ob="figobmps3Tnotablepathogenicvariantsinge">p.Val334Phe</a> or <a href="/books/NBK546574/table/mps3.T.notable_pathogenic_variants_in_ge/?report=objectonly" target="object" rid-ob="figobmps3Tnotablepathogenicvariantsinge">p.Pro521Leu</a> is associated with severe disease course [<a class="bibr" href="#mps3.REF.zhao.1998.53" rid="mps3.REF.zhao.1998.53">Zhao et al 1998</a>, <a class="bibr" href="#mps3.REF.weber.1999.34" rid="mps3.REF.weber.1999.34">Weber et al 1999</a>].</div></li><li class="half_rhythm"><div>The missense pathogenic variants <a href="/books/NBK546574/table/mps3.T.notable_pathogenic_variants_in_ge/?report=objectonly" target="object" rid-ob="figobmps3Tnotablepathogenicvariantsinge">p.Arg643Cys</a>, <a href="/books/NBK546574/table/mps3.T.notable_pathogenic_variants_in_ge/?report=objectonly" target="object" rid-ob="figobmps3Tnotablepathogenicvariantsinge">p.Ser612Gly</a>, <a href="/books/NBK546574/table/mps3.T.notable_pathogenic_variants_in_ge/?report=objectonly" target="object" rid-ob="figobmps3Tnotablepathogenicvariantsinge">p.Glu634Lys</a>, and <a href="/books/NBK546574/table/mps3.T.notable_pathogenic_variants_in_ge/?report=objectonly" target="object" rid-ob="figobmps3Tnotablepathogenicvariantsinge">p.Leu497Val</a> are only reported in individuals w/attenuated or slowly progressing phenotypes [<a class="bibr" href="#mps3.REF.valstar.2010b.759" rid="mps3.REF.valstar.2010b.759">Valstar et al 2010b</a>].</div></li></ul>
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</td></tr><tr><td headers="hd_h_mps3.T.genotypephenotype_correlations_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>SGSH</i><br />(MPS IIIA)</td><td headers="hd_h_mps3.T.genotypephenotype_correlations_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<ul><li class="half_rhythm"><div>Homozygotes or compound heterozygotes for variants <a href="/books/NBK546574/table/mps3.T.notable_pathogenic_variants_in_ge/?report=objectonly" target="object" rid-ob="figobmps3Tnotablepathogenicvariantsinge">p.Arg245His</a>, <a href="/books/NBK546574/table/mps3.T.notable_pathogenic_variants_in_ge/?report=objectonly" target="object" rid-ob="figobmps3Tnotablepathogenicvariantsinge">p.Arg74Cys</a>, <a href="/books/NBK546574/table/mps3.T.notable_pathogenic_variants_in_ge/?report=objectonly" target="object" rid-ob="figobmps3Tnotablepathogenicvariantsinge">p.Gln380Arg</a>, <a href="/books/NBK546574/table/mps3.T.notable_pathogenic_variants_in_ge/?report=objectonly" target="object" rid-ob="figobmps3Tnotablepathogenicvariantsinge">p.Ser66Trp</a>, and <a href="/books/NBK546574/table/mps3.T.notable_pathogenic_variants_in_ge/?report=objectonly" target="object" rid-ob="figobmps3Tnotablepathogenicvariantsinge">p.Val361SerfsTer52</a> (c.1080delC) have rapidly progressing disease course [<a class="bibr" href="#mps3.REF.meyer.2008.770" rid="mps3.REF.meyer.2008.770">Meyer et al 2008</a>, <a class="bibr" href="#mps3.REF.valstar.2010c.876" rid="mps3.REF.valstar.2010c.876">Valstar et al 2010c</a>].</div></li><li class="half_rhythm"><div>The missense <a href="/books/NBK546574/table/mps3.T.notable_pathogenic_variants_in_ge/?report=objectonly" target="object" rid-ob="figobmps3Tnotablepathogenicvariantsinge">p.Ser298Pro</a> variant is associated with a slowly progressive disease course [<a class="bibr" href="#mps3.REF.meyer.2008.770" rid="mps3.REF.meyer.2008.770">Meyer et al 2008</a>, <a class="bibr" href="#mps3.REF.valstar.2010c.876" rid="mps3.REF.valstar.2010c.876">Valstar et al 2010c</a>].</div></li></ul>
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</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobmps3Talternatenamingsystemformpsi"><div id="mps3.T.alternate_naming_system_for_mps_i" class="table"><h3><span class="label">Table 3. </span></h3><div class="caption"><p>Alternate Naming System for MPS III-Related Enzymes</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK546574/table/mps3.T.alternate_naming_system_for_mps_i/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__mps3.T.alternate_naming_system_for_mps_i_lrgtbl__"><table><thead><tr><th id="hd_h_mps3.T.alternate_naming_system_for_mps_i_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">MPS III Subtype</th><th id="hd_h_mps3.T.alternate_naming_system_for_mps_i_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">UniProt Knowledgebase (UniProtKB) Name</th><th id="hd_h_mps3.T.alternate_naming_system_for_mps_i_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Alternative Enzyme Name</th></tr></thead><tbody><tr><td headers="hd_h_mps3.T.alternate_naming_system_for_mps_i_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">MPS IIIA</td><td headers="hd_h_mps3.T.alternate_naming_system_for_mps_i_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">N-sulphoglucosamine sulphohydrolase</td><td headers="hd_h_mps3.T.alternate_naming_system_for_mps_i_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Heparan-N-sulfatase; sulfamidase; sulfamate sulfohydrolase</td></tr><tr><td headers="hd_h_mps3.T.alternate_naming_system_for_mps_i_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">MPS IIIB</td><td headers="hd_h_mps3.T.alternate_naming_system_for_mps_i_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Alpha-N-acetylglucosaminidase</td><td headers="hd_h_mps3.T.alternate_naming_system_for_mps_i_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">N-acetyl-alpha-D-glucosaminidase</td></tr><tr><td headers="hd_h_mps3.T.alternate_naming_system_for_mps_i_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">MPS IIIC</td><td headers="hd_h_mps3.T.alternate_naming_system_for_mps_i_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Heparan-alpha-glucosaminide N-acetyltransferase</td><td headers="hd_h_mps3.T.alternate_naming_system_for_mps_i_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Acetyl CoA: alpha-glucosamine N-acetyltransferase</td></tr><tr><td headers="hd_h_mps3.T.alternate_naming_system_for_mps_i_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">MPS IIID</td><td headers="hd_h_mps3.T.alternate_naming_system_for_mps_i_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">N-acetylglucosamine-6-sulfatase</td><td headers="hd_h_mps3.T.alternate_naming_system_for_mps_i_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Glucosamine-6-sulfatase</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobmps3Tgenesofinterestinthedifferen"><div id="mps3.T.genes_of_interest_in_the_differen" class="table"><h3><span class="label">Table 4. </span></h3><div class="caption"><p>Genes of Interest in the Differential Diagnosis of Mucopolysaccharidosis Type III</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK546574/table/mps3.T.genes_of_interest_in_the_differen/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__mps3.T.genes_of_interest_in_the_differen_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_mps3.T.genes_of_interest_in_the_differen_1_1_1_1" rowspan="2" scope="col" colspan="1" headers="hd_h_mps3.T.genes_of_interest_in_the_differen_1_1_1_1" style="text-align:left;vertical-align:middle;">Gene</th><th id="hd_h_mps3.T.genes_of_interest_in_the_differen_1_1_1_2" rowspan="2" scope="col" colspan="1" headers="hd_h_mps3.T.genes_of_interest_in_the_differen_1_1_1_2" style="text-align:left;vertical-align:middle;">DiffDx<br />Disorder</th><th id="hd_h_mps3.T.genes_of_interest_in_the_differen_1_1_1_3" rowspan="2" scope="col" colspan="1" headers="hd_h_mps3.T.genes_of_interest_in_the_differen_1_1_1_3" style="text-align:left;vertical-align:middle;">MOI</th><th id="hd_h_mps3.T.genes_of_interest_in_the_differen_1_1_1_4" colspan="2" scope="colgroup" rowspan="1" style="text-align:center;vertical-align:middle;">Clinical Features of DiffDx Disorder</th></tr><tr><th headers="hd_h_mps3.T.genes_of_interest_in_the_differen_1_1_1_4" id="hd_h_mps3.T.genes_of_interest_in_the_differen_1_1_2_1" colspan="1" scope="colgroup" rowspan="1" style="text-align:left;vertical-align:middle;">Overlapping w/MPS III</th><th headers="hd_h_mps3.T.genes_of_interest_in_the_differen_1_1_1_4" id="hd_h_mps3.T.genes_of_interest_in_the_differen_1_1_2_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Distinguishing from MPS III</th></tr></thead><tbody><tr><td headers="hd_h_mps3.T.genes_of_interest_in_the_differen_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>GNPTAB</i>
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</td><td headers="hd_h_mps3.T.genes_of_interest_in_the_differen_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="/books/n/gene/ml2/?report=reader">ML II</a>
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</td><td headers="hd_h_mps3.T.genes_of_interest_in_the_differen_1_1_1_3" rowspan="2" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_mps3.T.genes_of_interest_in_the_differen_1_1_1_4 hd_h_mps3.T.genes_of_interest_in_the_differen_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<ul><li class="half_rhythm"><div>Coarse facies</div></li><li class="half_rhythm"><div>Frequent ear infections</div></li><li class="half_rhythm"><div>Inguinal & umbilical hernias</div></li></ul>
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</td><td headers="hd_h_mps3.T.genes_of_interest_in_the_differen_1_1_1_4 hd_h_mps3.T.genes_of_interest_in_the_differen_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<ul><li class="half_rhythm"><div>Dysostosis multiplex</div></li><li class="half_rhythm"><div>Corneal clouding</div></li><li class="half_rhythm"><div>Significant DD seen in 1st year of life</div></li><li class="half_rhythm"><div>Death at age ~2 yrs from neurologic decline & multisystem involvement</div></li></ul>
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</td></tr><tr><td headers="hd_h_mps3.T.genes_of_interest_in_the_differen_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">
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<a href="/books/n/gene/ml2/?report=reader">ML III alpha/beta</a>
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</td><td headers="hd_h_mps3.T.genes_of_interest_in_the_differen_1_1_1_4 hd_h_mps3.T.genes_of_interest_in_the_differen_1_1_2_1" colspan="1" rowspan="1" style="text-align:left;vertical-align:middle;">
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<ul><li class="half_rhythm"><div>Coarse facies</div></li><li class="half_rhythm"><div>Frequent upper-respiratory & ear infections</div></li></ul>
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</td><td headers="hd_h_mps3.T.genes_of_interest_in_the_differen_1_1_1_4 hd_h_mps3.T.genes_of_interest_in_the_differen_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<ul><li class="half_rhythm"><div>Dysostosis multiplex</div></li><li class="half_rhythm"><div>Slight corneal clouding</div></li><li class="half_rhythm"><div>Normal to mildly impaired cognitive development</div></li></ul>
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</td></tr><tr><td headers="hd_h_mps3.T.genes_of_interest_in_the_differen_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>IDUA</i>
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</td><td headers="hd_h_mps3.T.genes_of_interest_in_the_differen_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="/books/n/gene/mps1/?report=reader">MPS I</a>
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</td><td headers="hd_h_mps3.T.genes_of_interest_in_the_differen_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_mps3.T.genes_of_interest_in_the_differen_1_1_1_4 hd_h_mps3.T.genes_of_interest_in_the_differen_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<ul><li class="half_rhythm"><div>Coarse facies</div></li><li class="half_rhythm"><div>Frequent upper-respiratory & ear infections</div></li><li class="half_rhythm"><div>Inguinal & umbilical hernias</div></li><li class="half_rhythm"><div>DD & cognitive decline in severe form of disease</div></li><li class="half_rhythm"><div>Hepatosplenomegaly</div></li></ul>
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</td><td headers="hd_h_mps3.T.genes_of_interest_in_the_differen_1_1_1_4 hd_h_mps3.T.genes_of_interest_in_the_differen_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<ul><li class="half_rhythm"><div>Dysostosis multiplex</div></li><li class="half_rhythm"><div>Placid behavior in contrast to aggressive or hyperactive</div></li><li class="half_rhythm"><div>Abnormal heparan & dermatan sulfate in urine GAG analysis</div></li><li class="half_rhythm"><div>Corneal clouding</div></li><li class="half_rhythm"><div>Hydrocephalus</div></li></ul>
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</td></tr><tr><td headers="hd_h_mps3.T.genes_of_interest_in_the_differen_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>IDS</i>
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</td><td headers="hd_h_mps3.T.genes_of_interest_in_the_differen_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="/books/n/gene/hunter/?report=reader">MPS II</a>
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</td><td headers="hd_h_mps3.T.genes_of_interest_in_the_differen_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">XL</td><td headers="hd_h_mps3.T.genes_of_interest_in_the_differen_1_1_1_4 hd_h_mps3.T.genes_of_interest_in_the_differen_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<ul><li class="half_rhythm"><div>Coarse facies</div></li><li class="half_rhythm"><div>Frequent upper-respiratory & ear infections</div></li><li class="half_rhythm"><div>Inguinal & umbilical hernias</div></li><li class="half_rhythm"><div>DD & cognitive decline in severe form of disease</div></li><li class="half_rhythm"><div>Behavioral abnormalities</div></li><li class="half_rhythm"><div>Hepatosplenomegaly</div></li></ul>
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</td><td headers="hd_h_mps3.T.genes_of_interest_in_the_differen_1_1_1_4 hd_h_mps3.T.genes_of_interest_in_the_differen_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<ul><li class="half_rhythm"><div>Dysostosis multiplex</div></li><li class="half_rhythm"><div>Observed almost exclusively in males</div></li><li class="half_rhythm"><div>Abnormal heparan & dermatan sulfate in urine GAG analysis</div></li><li class="half_rhythm"><div>Hydrocephalus</div></li></ul>
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</td></tr><tr><td headers="hd_h_mps3.T.genes_of_interest_in_the_differen_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>SUMF1</i>
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</td><td headers="hd_h_mps3.T.genes_of_interest_in_the_differen_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="/books/n/gene/m-sulfatase-def/?report=reader">Multiple sulfatase deficiency</a>
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</td><td headers="hd_h_mps3.T.genes_of_interest_in_the_differen_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_mps3.T.genes_of_interest_in_the_differen_1_1_1_4 hd_h_mps3.T.genes_of_interest_in_the_differen_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<ul><li class="half_rhythm"><div>Hepatosplenomegaly</div></li><li class="half_rhythm"><div>DD & cognitive impairment</div></li><li class="half_rhythm"><div>Psychomotor regression</div></li><li class="half_rhythm"><div>Hirsutism</div></li><li class="half_rhythm"><div>Coarse facies</div></li></ul>
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</td><td headers="hd_h_mps3.T.genes_of_interest_in_the_differen_1_1_1_4 hd_h_mps3.T.genes_of_interest_in_the_differen_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<ul><li class="half_rhythm"><div>Ichthyosis</div></li><li class="half_rhythm"><div>Abnormal enzymatic activity for multiple sulfatases</div></li></ul>
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</td></tr><tr><td headers="hd_h_mps3.T.genes_of_interest_in_the_differen_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>RAI1</i>
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</td><td headers="hd_h_mps3.T.genes_of_interest_in_the_differen_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="/books/n/gene/sms/?report=reader">Smith-Magenis syndrome</a>
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</td><td headers="hd_h_mps3.T.genes_of_interest_in_the_differen_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">See footnote 1</td><td headers="hd_h_mps3.T.genes_of_interest_in_the_differen_1_1_1_4 hd_h_mps3.T.genes_of_interest_in_the_differen_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<ul><li class="half_rhythm"><div>Speech delay</div></li><li class="half_rhythm"><div>DD & cognitive impairment</div></li><li class="half_rhythm"><div>Sleep disturbance</div></li><li class="half_rhythm"><div>Behavioral outbursts</div></li><li class="half_rhythm"><div>Hyperactivity</div></li></ul>
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</td><td headers="hd_h_mps3.T.genes_of_interest_in_the_differen_1_1_1_4 hd_h_mps3.T.genes_of_interest_in_the_differen_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<ul><li class="half_rhythm"><div>Infantile hypotonia & failure to thrive</div></li><li class="half_rhythm"><div>Mild-to-moderate ID w/out regression</div></li><li class="half_rhythm"><div>Characteristic dysmorphic facies</div></li><li class="half_rhythm"><div>Stereotypic "lick & flip" & "self-hug" behaviors</div></li></ul>
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</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">AR = autosomal recessive; DD = developmental delay; DiffDx = differential diagnosis; ID = intellectual disability; ML = mucolipidosis; MOI = mode of inheritance; MPS = mucopolysaccharidosis; XL = X-linked</p></div></dd></dl><dl class="bkr_refwrap"><dt>1. </dt><dd><div id="mps3.TF.4.1"><p class="no_margin">Smith-Magenis syndrome is caused either by a 17p11.2 deletion that includes <i>RAI1</i> or, less commonly, by a pathogenic variant in <i>RAI1</i>. Virtually all occurrences are <i>de novo.</i></p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobmps3Trecommendedevaluationsfollowing"><div id="mps3.T.recommended_evaluations_following" class="table"><h3><span class="label">Table 5. </span></h3><div class="caption"><p>Recommended Evaluations Following Initial Diagnosis in Individuals with Mucopolysaccharidosis Type III</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK546574/table/mps3.T.recommended_evaluations_following/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__mps3.T.recommended_evaluations_following_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_mps3.T.recommended_evaluations_following_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">System/Concern</th><th id="hd_h_mps3.T.recommended_evaluations_following_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Evaluation</th><th id="hd_h_mps3.T.recommended_evaluations_following_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Comment</th></tr></thead><tbody><tr><td headers="hd_h_mps3.T.recommended_evaluations_following_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Constitutional</b>
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</td><td headers="hd_h_mps3.T.recommended_evaluations_following_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Abdominal ultrasound</td><td headers="hd_h_mps3.T.recommended_evaluations_following_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Evaluate for hepatosplenomegaly.</td></tr><tr><td headers="hd_h_mps3.T.recommended_evaluations_following_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Neurologic</b>
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</td><td headers="hd_h_mps3.T.recommended_evaluations_following_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Neurologic examination &/or referral to pediatric neurologist</td><td headers="hd_h_mps3.T.recommended_evaluations_following_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Consider EEG if seizures are a concern.</td></tr><tr><td headers="hd_h_mps3.T.recommended_evaluations_following_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Brain MRI</td><td headers="hd_h_mps3.T.recommended_evaluations_following_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Evaluate for abnormalities incl hydrocephalus.</td></tr><tr><td headers="hd_h_mps3.T.recommended_evaluations_following_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Language</b>
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</td><td headers="hd_h_mps3.T.recommended_evaluations_following_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Speech & language eval</td><td headers="hd_h_mps3.T.recommended_evaluations_following_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Delayed to absent acquisition of language</td></tr><tr><td headers="hd_h_mps3.T.recommended_evaluations_following_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Development</b>
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</td><td headers="hd_h_mps3.T.recommended_evaluations_following_1_1_1_2" rowspan="2" colspan="1" style="text-align:left;vertical-align:middle;">Developmental assessment</td><td headers="hd_h_mps3.T.recommended_evaluations_following_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To incl motor, adaptive, cognitive, & speech/language eval</td></tr><tr><td headers="hd_h_mps3.T.recommended_evaluations_following_1_1_1_3" colspan="1" scope="col" rowspan="1" style="text-align:left;vertical-align:middle;">Assess need for early intervention / special education.</td></tr><tr><td headers="hd_h_mps3.T.recommended_evaluations_following_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Psychiatric/</b>
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<br />
|
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<b>Behavioral</b>
|
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</td><td headers="hd_h_mps3.T.recommended_evaluations_following_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Referral to psychiatrist</td><td headers="hd_h_mps3.T.recommended_evaluations_following_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Evaluate for behavioral concerns incl sleep disturbances, hyperactivity, aggressiveness, low frustration tolerance, & ASD-like behaviors.</td></tr><tr><td headers="hd_h_mps3.T.recommended_evaluations_following_1_1_1_1" rowspan="3" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Musculoskeletal</b>
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</td><td headers="hd_h_mps3.T.recommended_evaluations_following_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Skeletal survey & referral to orthopedist</td><td headers="hd_h_mps3.T.recommended_evaluations_following_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Incl eval for osteonecrosis of femoral head, abnormal vertebra causing ↑ risk for scoliosis, & risk for carpal tunnel syndrome.</td></tr><tr><td headers="hd_h_mps3.T.recommended_evaluations_following_1_1_1_2" colspan="1" scope="col" rowspan="1" style="text-align:left;vertical-align:middle;">DXA & vitamin D metabolism studies to assess BMD</td><td headers="hd_h_mps3.T.recommended_evaluations_following_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_mps3.T.recommended_evaluations_following_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Referral for PT/OT</td><td headers="hd_h_mps3.T.recommended_evaluations_following_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Evaluate & assess mobility & activities of daily living.</td></tr><tr><td headers="hd_h_mps3.T.recommended_evaluations_following_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Hearing</b>
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</td><td headers="hd_h_mps3.T.recommended_evaluations_following_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Audiogram & referral to otolaryngologist</td><td headers="hd_h_mps3.T.recommended_evaluations_following_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Evaluate for conductive & sensorineural hearing loss.</td></tr><tr><td headers="hd_h_mps3.T.recommended_evaluations_following_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Respiratory</b>
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</td><td headers="hd_h_mps3.T.recommended_evaluations_following_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Referral to pulmonologist</td><td headers="hd_h_mps3.T.recommended_evaluations_following_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Evaluate for sleep apnea, wheezing.</td></tr><tr><td headers="hd_h_mps3.T.recommended_evaluations_following_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Gastrointestinal</b>
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</td><td headers="hd_h_mps3.T.recommended_evaluations_following_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Assessment of swallowing, feeding, & nutritional status, particularly in later stages of disease</td><td headers="hd_h_mps3.T.recommended_evaluations_following_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_mps3.T.recommended_evaluations_following_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Cardiovascular</b>
|
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</td><td headers="hd_h_mps3.T.recommended_evaluations_following_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Echocardiogram</td><td headers="hd_h_mps3.T.recommended_evaluations_following_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Evaluate for valvular disease & other cardiac anomalies.</td></tr><tr><td headers="hd_h_mps3.T.recommended_evaluations_following_1_1_1_1" rowspan="3" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Miscellaneous/</b>
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<br />
|
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<b>Other</b>
|
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</td><td headers="hd_h_mps3.T.recommended_evaluations_following_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Family support/resources</td><td headers="hd_h_mps3.T.recommended_evaluations_following_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Community or <a href="#mps3.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>. Social work involvement for parental support.</td></tr><tr><td headers="hd_h_mps3.T.recommended_evaluations_following_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Consultation w/clinical geneticist &/or genetic counselor</td><td headers="hd_h_mps3.T.recommended_evaluations_following_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To incl genetic counseling</td></tr><tr><td headers="hd_h_mps3.T.recommended_evaluations_following_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Referral to palliative care specialist</td><td headers="hd_h_mps3.T.recommended_evaluations_following_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">When deemed appropriate by family & care providers</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">ASD = autism spectrum disorder; BMD = bone mineral density; DXA = dual-energy x-ray absorptiometry; OT = occupational therapist; PT = physical therapist</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobmps3Ttreatmentofmanifestationsinin"><div id="mps3.T.treatment_of_manifestations_in_in" class="table"><h3><span class="label">Table 6. </span></h3><div class="caption"><p>Treatment of Manifestations in Individuals with Mucopolysaccharidosis Type III</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK546574/table/mps3.T.treatment_of_manifestations_in_in/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__mps3.T.treatment_of_manifestations_in_in_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_mps3.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_mps3.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_mps3.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_mps3.T.treatment_of_manifestations_in_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Seizures</b>
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</td><td headers="hd_h_mps3.T.treatment_of_manifestations_in_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">ASM as determined by neurologist</td><td headers="hd_h_mps3.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_mps3.T.treatment_of_manifestations_in_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Neurodevelopmental delays</b>
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</td><td headers="hd_h_mps3.T.treatment_of_manifestations_in_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Supportive therapies (e.g., speech therapy, PT, OT)</td><td headers="hd_h_mps3.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_mps3.T.treatment_of_manifestations_in_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Psychiatric/</b>
|
|
<br />
|
|
<b>behavioral issues</b>
|
|
</td><td headers="hd_h_mps3.T.treatment_of_manifestations_in_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<ul><li class="half_rhythm"><div>Treatment as determined by psychiatrist</div></li><li class="half_rhythm"><div>Creation of physically safe environment at home</div></li></ul>
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</td><td headers="hd_h_mps3.T.treatment_of_manifestations_in_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Behavioral therapy is unlikely to be effective, especially since any improvements are often lost w/disease progression. Risperidone can be considered for treatment of hyperactivity [<a class="bibr" href="#mps3.REF.kalkan_ucar.2010.156" rid="mps3.REF.kalkan_ucar.2010.156">Kalkan Ucar et al 2010</a>]. Antipsychotic drugs may also be effective.</td></tr><tr><td headers="hd_h_mps3.T.treatment_of_manifestations_in_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Sleep disorders</b>
|
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</td><td headers="hd_h_mps3.T.treatment_of_manifestations_in_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<ul><li class="half_rhythm"><div>Consider use of melatonin or other medication [<a class="bibr" href="#mps3.REF.mahon.2014.e84128" rid="mps3.REF.mahon.2014.e84128">Mahon et al 2014</a>].</div></li><li class="half_rhythm"><div>Consider polysomnogram if suspicion of sleep apnea.</div></li></ul>
|
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</td><td headers="hd_h_mps3.T.treatment_of_manifestations_in_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Treating sleep disorders is, overall, difficult. Consider referral to pulmonologist if concern for sleep apnea. Home modifications may be helpful for children to avoid falls or injuries at night.</td></tr><tr><td headers="hd_h_mps3.T.treatment_of_manifestations_in_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
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<b>Musculoskeletal manifestations</b>
|
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</td><td headers="hd_h_mps3.T.treatment_of_manifestations_in_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
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<ul><li class="half_rhythm"><div>Treatment as determined by orthopedist</div></li><li class="half_rhythm"><div>PT or hydrotherapy for joint stiffness</div></li><li class="half_rhythm"><div>Vitamin D therapy in the context of low BMD [<a class="bibr" href="#mps3.REF.nur.2017.338" rid="mps3.REF.nur.2017.338">Nur et al 2017</a>]</div></li></ul>
|
|
</td><td headers="hd_h_mps3.T.treatment_of_manifestations_in_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Decisions about surgical intervention should be made in the context of disease course & quality of life. Therapies may be useful, but should not be intensive, especially if they cause pain.</td></tr><tr><td headers="hd_h_mps3.T.treatment_of_manifestations_in_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Hearing loss</b>
|
|
</td><td headers="hd_h_mps3.T.treatment_of_manifestations_in_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Ear tube insertion or hearing aid use</td><td headers="hd_h_mps3.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_mps3.T.treatment_of_manifestations_in_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Recurrent ENT/respiratory infections</b>
|
|
</td><td headers="hd_h_mps3.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>Treatment as determined by otolaryngologist</div></li><li class="half_rhythm"><div>Consider airway clearance therapy, particularly in later disease stages.</div></li></ul>
|
|
</td><td headers="hd_h_mps3.T.treatment_of_manifestations_in_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
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<ul><li class="half_rhythm"><div>The importance of routine immunizations & annual influenza vaccines should be emphasized.</div></li><li class="half_rhythm"><div>Pneumococcal vaccine may be considered.</div></li></ul>
|
|
</td></tr><tr><td headers="hd_h_mps3.T.treatment_of_manifestations_in_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
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<b>Cardiovascular anomalies</b>
|
|
</td><td headers="hd_h_mps3.T.treatment_of_manifestations_in_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Treatment as determined by cardiologist</td><td headers="hd_h_mps3.T.treatment_of_manifestations_in_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Consider bacterial endocarditis prophylaxis for patients w/cardiac abnormalities.</td></tr><tr><td headers="hd_h_mps3.T.treatment_of_manifestations_in_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Feeding difficulties</b>
|
|
<br />
|
|
<b>w/resulting malnutrition</b>
|
|
</td><td headers="hd_h_mps3.T.treatment_of_manifestations_in_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Gastrostomy tube (G-tube) placement</td><td headers="hd_h_mps3.T.treatment_of_manifestations_in_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Difficulty chewing & swallowing, &/or dysphagia are common in later stages of disease. Aspiration may ↑ risk for pulmonary infection.</td></tr><tr><td headers="hd_h_mps3.T.treatment_of_manifestations_in_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
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<b>Visual impairment</b>
|
|
</td><td headers="hd_h_mps3.T.treatment_of_manifestations_in_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Treatment as determined by ophthalmologist</td><td headers="hd_h_mps3.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_mps3.T.treatment_of_manifestations_in_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
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<b>Palliative care specialist</b>
|
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</td><td headers="hd_h_mps3.T.treatment_of_manifestations_in_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Per palliative care specialist</td><td headers="hd_h_mps3.T.treatment_of_manifestations_in_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">See <a href="#mps3.Palliative_Care">Palliative Care</a>.</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">ASM = anti-seizure medication; BMD = bone mineral density; OT = occupational therapy; PT = physical therapy</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobmps3Trecommendedsurveillanceforindi"><div id="mps3.T.recommended_surveillance_for_indi" class="table"><h3><span class="label">Table 7. </span></h3><div class="caption"><p>Recommended Surveillance for Individuals with Mucopolysaccharidosis Type III</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK546574/table/mps3.T.recommended_surveillance_for_indi/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__mps3.T.recommended_surveillance_for_indi_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_mps3.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_mps3.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_mps3.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_mps3.T.recommended_surveillance_for_indi_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
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<b>Neurologic</b>
|
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</td><td headers="hd_h_mps3.T.recommended_surveillance_for_indi_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Monitor treatment effectiveness in those w/seizures.</td><td headers="hd_h_mps3.T.recommended_surveillance_for_indi_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">As clinically indicated</td></tr><tr><td headers="hd_h_mps3.T.recommended_surveillance_for_indi_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
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<b>Development</b>
|
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</td><td headers="hd_h_mps3.T.recommended_surveillance_for_indi_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Monitor developmental capabilities & educational needs.</td><td headers="hd_h_mps3.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_mps3.T.recommended_surveillance_for_indi_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
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<b>Psychiatric/</b>
|
|
<br />
|
|
<b>Behavioral issues</b>
|
|
</td><td headers="hd_h_mps3.T.recommended_surveillance_for_indi_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Assessment of destructive or disruptive behaviors</td><td headers="hd_h_mps3.T.recommended_surveillance_for_indi_1_1_1_3" rowspan="2" colspan="1" style="text-align:left;vertical-align:middle;">As clinically indicated</td></tr><tr><td headers="hd_h_mps3.T.recommended_surveillance_for_indi_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_mps3.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 joint mobility; assessment by orthopedist.</div></li><li class="half_rhythm"><div>Monitor BMD w/DXA & vitamin D metabolism studies.</div></li></ul>
|
|
</td></tr><tr><td headers="hd_h_mps3.T.recommended_surveillance_for_indi_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Hearing</b>
|
|
</td><td headers="hd_h_mps3.T.recommended_surveillance_for_indi_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Assessment by audiologist & otolaryngologist</td><td headers="hd_h_mps3.T.recommended_surveillance_for_indi_1_1_1_3" rowspan="2" colspan="1" style="text-align:left;vertical-align:middle;">Annually</td></tr><tr><td headers="hd_h_mps3.T.recommended_surveillance_for_indi_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
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<b>Cardiovascular</b>
|
|
</td><td headers="hd_h_mps3.T.recommended_surveillance_for_indi_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Echocardiogram & EKG to assess for valvular disease & conduction system defects</td></tr><tr><td headers="hd_h_mps3.T.recommended_surveillance_for_indi_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Ocular</b>
|
|
</td><td headers="hd_h_mps3.T.recommended_surveillance_for_indi_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Ophthalmologic assessment</td><td headers="hd_h_mps3.T.recommended_surveillance_for_indi_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">As clinically indicated</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">BMD = bone mineral density; DXA = dual-energy x-ray absorptiometry</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobmps3molgenTA"><div id="mps3.molgen.TA" class="table"><h3><span class="label">Table A.</span></h3><div class="caption"><p>Mucopolysaccharidosis Type III: Genes and Databases</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK546574/table/mps3.molgen.TA/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__mps3.molgen.TA_lrgtbl__"><table class="no_bottom_margin"><tbody><tr><th id="hd_b_mps3.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">Gene</th><th id="hd_b_mps3.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">Chromosome Locus</th><th id="hd_b_mps3.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">Protein</th><th id="hd_b_mps3.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">Locus-Specific Databases</th><th id="hd_b_mps3.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">HGMD</th><th id="hd_b_mps3.molgen.TA_1_1_1_6" rowspan="1" colspan="1" style="vertical-align:top;">ClinVar</th></tr><tr><td headers="hd_b_mps3.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="/gene/2799" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=gene">
|
|
<i>GNS</i>
|
|
</a>
|
|
</td><td headers="hd_b_mps3.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=2799" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">12q14<wbr style="display:inline-block"></wbr>​.3</a>
|
|
</td><td headers="hd_b_mps3.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="http://www.uniprot.org/uniprot/P15586" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">N-acetylglucosamine-6-sulfatase</a>
|
|
</td><td headers="hd_b_mps3.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="http://databases.lovd.nl/shared/genes/GNS" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">GNS database</a>
|
|
</td><td headers="hd_b_mps3.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="http://www.hgmd.cf.ac.uk/ac/gene.php?gene=GNS" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">GNS</a>
|
|
</td><td headers="hd_b_mps3.molgen.TA_1_1_1_6" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar/?term=GNS[gene]" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">GNS</a>
|
|
</td></tr><tr><td headers="hd_b_mps3.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="/gene/138050" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=gene">
|
|
<i>HGSNAT</i>
|
|
</a>
|
|
</td><td headers="hd_b_mps3.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=138050" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">8p11<wbr style="display:inline-block"></wbr>​.21-p11.1</a>
|
|
</td><td headers="hd_b_mps3.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="http://www.uniprot.org/uniprot/Q68CP4" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Heparan-alpha-glucosaminide N-acetyltransferase</a>
|
|
</td><td headers="hd_b_mps3.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="http://www.LOVD.nl/HGSNAT" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Heparan-alpha-glucosaminide N-acetyltransferase (HGSNAT) @ LOVD</a>
|
|
</td><td headers="hd_b_mps3.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="http://www.hgmd.cf.ac.uk/ac/gene.php?gene=HGSNAT" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">HGSNAT</a>
|
|
</td><td headers="hd_b_mps3.molgen.TA_1_1_1_6" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar/?term=HGSNAT[gene]" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">HGSNAT</a>
|
|
</td></tr><tr><td headers="hd_b_mps3.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="/gene/4669" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=gene">
|
|
<i>NAGLU</i>
|
|
</a>
|
|
</td><td headers="hd_b_mps3.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=4669" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">17q21<wbr style="display:inline-block"></wbr>​.2</a>
|
|
</td><td headers="hd_b_mps3.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="http://www.uniprot.org/uniprot/P54802" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Alpha-N-acetylglucosaminidase</a>
|
|
</td><td headers="hd_b_mps3.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="http://databases.lovd.nl/shared/genes/NAGLU" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NAGLU database</a>
|
|
</td><td headers="hd_b_mps3.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="http://www.hgmd.cf.ac.uk/ac/gene.php?gene=NAGLU" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NAGLU</a>
|
|
</td><td headers="hd_b_mps3.molgen.TA_1_1_1_6" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar/?term=NAGLU[gene]" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NAGLU</a>
|
|
</td></tr><tr><td headers="hd_b_mps3.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="/gene/6448" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=gene">
|
|
<i>SGSH</i>
|
|
</a>
|
|
</td><td headers="hd_b_mps3.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=6448" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">17q25<wbr style="display:inline-block"></wbr>​.3</a>
|
|
</td><td headers="hd_b_mps3.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="http://www.uniprot.org/uniprot/P51688" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">N-sulphoglucosamine sulphohydrolase</a>
|
|
</td><td headers="hd_b_mps3.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="http://databases.lovd.nl/shared/genes/SGSH" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">SGSH database</a>
|
|
</td><td headers="hd_b_mps3.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="http://www.hgmd.cf.ac.uk/ac/gene.php?gene=SGSH" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">SGSH</a>
|
|
</td><td headers="hd_b_mps3.molgen.TA_1_1_1_6" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar/?term=SGSH[gene]" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">SGSH</a>
|
|
</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div id="mps3.TFA.1"><p class="no_margin">Data are compiled from the following standard references: gene from
|
|
<a href="http://www.genenames.org/index.html" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">HGNC</a>;
|
|
chromosome locus 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/?report=reader">here</a>.</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobmps3molgenTB"><div id="mps3.molgen.TB" class="table"><h3><span class="label">Table B.</span></h3><div class="caption"><p>OMIM Entries for Mucopolysaccharidosis Type III (<a href="/omim/252900,252920,252930,252940,605270,607664,609701,610453" 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/NBK546574/table/mps3.molgen.TB/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__mps3.molgen.TB_lrgtbl__"><table><tbody><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<a href="/omim/252900" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">252900</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MUCOPOLYSACCHARIDOSIS, TYPE IIIA; MPS3A</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<a href="/omim/252920" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">252920</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MUCOPOLYSACCHARIDOSIS, TYPE IIIB; MPS3B</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<a href="/omim/252930" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">252930</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MUCOPOLYSACCHARIDOSIS, TYPE IIIC; MPS3C</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<a href="/omim/252940" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">252940</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MUCOPOLYSACCHARIDOSIS, TYPE IIID; MPS3D</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<a href="/omim/605270" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">605270</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">N-SULFOGLUCOSAMINE SULFOHYDROLASE; SGSH</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<a href="/omim/607664" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">607664</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">N-ACETYLGLUCOSAMINE-6-SULFATASE; GNS</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<a href="/omim/609701" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">609701</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">N-ACETYLGLUCOSAMINIDASE, ALPHA-; NAGLU</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<a href="/omim/610453" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">610453</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">HEPARAN-ALPHA-GLUCOSAMINIDE N-ACETYLTRANSFERASE; HGSNAT</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobmps3Tnotablepathogenicvariantsinge"><div id="mps3.T.notable_pathogenic_variants_in_ge" class="table"><h3><span class="label">Table 8. </span></h3><div class="caption"><p>Notable Pathogenic Variants in Genes Causing Mucopolysaccharidosis Type III</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK546574/table/mps3.T.notable_pathogenic_variants_in_ge/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__mps3.T.notable_pathogenic_variants_in_ge_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_mps3.T.notable_pathogenic_variants_in_ge_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_mps3.T.notable_pathogenic_variants_in_ge_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Reference Sequences</th><th id="hd_h_mps3.T.notable_pathogenic_variants_in_ge_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">DNA Nucleotide Change</th><th id="hd_h_mps3.T.notable_pathogenic_variants_in_ge_1_1_1_4" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Predicted Protein Change</th><th id="hd_h_mps3.T.notable_pathogenic_variants_in_ge_1_1_1_5" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Comment [Reference]</th></tr></thead><tbody><tr><td headers="hd_h_mps3.T.notable_pathogenic_variants_in_ge_1_1_1_1" rowspan="4" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<i>HGSNAT</i>
|
|
</td><td headers="hd_h_mps3.T.notable_pathogenic_variants_in_ge_1_1_1_2" rowspan="4" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_152419.3" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NM_152419<wbr style="display:inline-block"></wbr>​.3</a>
|
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<br />
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<a href="https://www.ncbi.nlm.nih.gov/protein/NP_689632.2" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NP_689632<wbr style="display:inline-block"></wbr>​.2</a>
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</td><td headers="hd_h_mps3.T.notable_pathogenic_variants_in_ge_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">c.1030C>T</td><td headers="hd_h_mps3.T.notable_pathogenic_variants_in_ge_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Arg384Ter</td><td headers="hd_h_mps3.T.notable_pathogenic_variants_in_ge_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Found in many populations [<a class="bibr" href="#mps3.REF.ruijter.2008.104" rid="mps3.REF.ruijter.2008.104">Ruijter et al 2008</a>]</td></tr><tr><td headers="hd_h_mps3.T.notable_pathogenic_variants_in_ge_1_1_1_3" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">c.784G>A</td><td headers="hd_h_mps3.T.notable_pathogenic_variants_in_ge_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Gly262Arg</td><td headers="hd_h_mps3.T.notable_pathogenic_variants_in_ge_1_1_1_5" rowspan="2" colspan="1" style="text-align:left;vertical-align:top;">2 compound heterozygous sisters w/significantly attenuated MPS IIIC [<a class="bibr" href="#mps3.REF.ruijter.2008.104" rid="mps3.REF.ruijter.2008.104">Ruijter et al 2008</a>]</td></tr><tr><td headers="hd_h_mps3.T.notable_pathogenic_variants_in_ge_1_1_1_3" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">c.1616C>G</td><td headers="hd_h_mps3.T.notable_pathogenic_variants_in_ge_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Ser539Cys</td></tr><tr><td headers="hd_h_mps3.T.notable_pathogenic_variants_in_ge_1_1_1_3" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">c.518G>A</td><td headers="hd_h_mps3.T.notable_pathogenic_variants_in_ge_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Gly173Asp</td><td headers="hd_h_mps3.T.notable_pathogenic_variants_in_ge_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">2 homozygous sibs w/KBS <sup>2</sup> [<a class="bibr" href="#mps3.REF.hu.2017.253" rid="mps3.REF.hu.2017.253">Hu et al 2017</a>]</td></tr><tr><td headers="hd_h_mps3.T.notable_pathogenic_variants_in_ge_1_1_1_1" rowspan="8" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>NAGLU</i>
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</td><td headers="hd_h_mps3.T.notable_pathogenic_variants_in_ge_1_1_1_2" rowspan="8" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_000263.4" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NM_000263<wbr style="display:inline-block"></wbr>​.4</a>
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<br />
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<a href="https://www.ncbi.nlm.nih.gov/protein/NP_000254.2" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NP_000254<wbr style="display:inline-block"></wbr>​.2</a>
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</td><td headers="hd_h_mps3.T.notable_pathogenic_variants_in_ge_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">c.889C>T</td><td headers="hd_h_mps3.T.notable_pathogenic_variants_in_ge_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Arg297Ter</td><td headers="hd_h_mps3.T.notable_pathogenic_variants_in_ge_1_1_1_5" rowspan="3" colspan="1" style="text-align:left;vertical-align:middle;">Homozygotes w/severe MPS IIIB [<a class="bibr" href="#mps3.REF.zhao.1998.53" rid="mps3.REF.zhao.1998.53">Zhao et al 1998</a>, <a class="bibr" href="#mps3.REF.weber.1999.34" rid="mps3.REF.weber.1999.34">Weber et al 1999</a>, <a class="bibr" href="#mps3.REF.valstar.2010b.759" rid="mps3.REF.valstar.2010b.759">Valstar et al 2010b</a>]</td></tr><tr><td headers="hd_h_mps3.T.notable_pathogenic_variants_in_ge_1_1_1_3" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">c.1000G>T</td><td headers="hd_h_mps3.T.notable_pathogenic_variants_in_ge_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Val334Phe</td></tr><tr><td headers="hd_h_mps3.T.notable_pathogenic_variants_in_ge_1_1_1_3" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">c.1562C>T</td><td headers="hd_h_mps3.T.notable_pathogenic_variants_in_ge_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Pro521Leu</td></tr><tr><td headers="hd_h_mps3.T.notable_pathogenic_variants_in_ge_1_1_1_3" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">c.1927C>T</td><td headers="hd_h_mps3.T.notable_pathogenic_variants_in_ge_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Arg643Cys</td><td headers="hd_h_mps3.T.notable_pathogenic_variants_in_ge_1_1_1_5" rowspan="4" colspan="1" style="text-align:left;vertical-align:middle;">Compound heterozygotes or homozygotes w/attenuated MPS IIIB [<a class="bibr" href="#mps3.REF.valstar.2010b.759" rid="mps3.REF.valstar.2010b.759">Valstar et al 2010b</a>]</td></tr><tr><td headers="hd_h_mps3.T.notable_pathogenic_variants_in_ge_1_1_1_3" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">c.1834A>G</td><td headers="hd_h_mps3.T.notable_pathogenic_variants_in_ge_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Ser612Gly</td></tr><tr><td headers="hd_h_mps3.T.notable_pathogenic_variants_in_ge_1_1_1_3" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">c.1900G>A</td><td headers="hd_h_mps3.T.notable_pathogenic_variants_in_ge_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Glu634Lys</td></tr><tr><td headers="hd_h_mps3.T.notable_pathogenic_variants_in_ge_1_1_1_3" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">c.1489C>G</td><td headers="hd_h_mps3.T.notable_pathogenic_variants_in_ge_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Leu497Val</td></tr><tr><td headers="hd_h_mps3.T.notable_pathogenic_variants_in_ge_1_1_1_3" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">c.529C>T</td><td headers="hd_h_mps3.T.notable_pathogenic_variants_in_ge_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Arg117Trp</td><td headers="hd_h_mps3.T.notable_pathogenic_variants_in_ge_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Compound heterozygous sibs w/extremely attenuated MPS IIIB [<a class="bibr" href="#mps3.REF.verhoeven.2010.162" rid="mps3.REF.verhoeven.2010.162">Verhoeven et al 2010</a>]</td></tr><tr><td headers="hd_h_mps3.T.notable_pathogenic_variants_in_ge_1_1_1_1" rowspan="6" scope="row" colspan="1" style="text-align:left;vertical-align:middle;"><i>SGSH</i> <sup>3</sup></td><td headers="hd_h_mps3.T.notable_pathogenic_variants_in_ge_1_1_1_2" rowspan="6" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_000199.5" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NM_000199<wbr style="display:inline-block"></wbr>​.5</a>
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<br />
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<a href="https://www.ncbi.nlm.nih.gov/protein/NP_000190.1" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NP_000190<wbr style="display:inline-block"></wbr>​.1</a>
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</td><td headers="hd_h_mps3.T.notable_pathogenic_variants_in_ge_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">c.220C>T</td><td headers="hd_h_mps3.T.notable_pathogenic_variants_in_ge_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Arg74Cys</td><td headers="hd_h_mps3.T.notable_pathogenic_variants_in_ge_1_1_1_5" rowspan="4" colspan="1" style="text-align:left;vertical-align:middle;">Homozygotes w/rapidly progressing MPS IIIA [<a class="bibr" href="#mps3.REF.valstar.2010c.876" rid="mps3.REF.valstar.2010c.876">Valstar et al 2010c</a>]</td></tr><tr><td headers="hd_h_mps3.T.notable_pathogenic_variants_in_ge_1_1_1_3" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">c.1139A>G</td><td headers="hd_h_mps3.T.notable_pathogenic_variants_in_ge_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Gln380Arg</td></tr><tr><td headers="hd_h_mps3.T.notable_pathogenic_variants_in_ge_1_1_1_3" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">c.197C>G</td><td headers="hd_h_mps3.T.notable_pathogenic_variants_in_ge_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Ser66Trp</td></tr><tr><td headers="hd_h_mps3.T.notable_pathogenic_variants_in_ge_1_1_1_3" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">c.1080delC</td><td headers="hd_h_mps3.T.notable_pathogenic_variants_in_ge_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Val361SerfsTer52</td></tr><tr><td headers="hd_h_mps3.T.notable_pathogenic_variants_in_ge_1_1_1_3" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">c.734G>A <sup>4</sup></td><td headers="hd_h_mps3.T.notable_pathogenic_variants_in_ge_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Arg245His</td><td headers="hd_h_mps3.T.notable_pathogenic_variants_in_ge_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<ul><li class="half_rhythm"><div>Homozygotes w/rapidly progressing MPS IIIA</div></li><li class="half_rhythm"><div>Common in northern European populations & founder variant in the Cayman Islands [<a class="bibr" href="#mps3.REF.rady.2002.211" rid="mps3.REF.rady.2002.211">Rady et al 2002</a>, <a class="bibr" href="#mps3.REF.meyer.2008.770" rid="mps3.REF.meyer.2008.770">Meyer et al 2008</a>]</div></li></ul>
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</td></tr><tr><td headers="hd_h_mps3.T.notable_pathogenic_variants_in_ge_1_1_1_3" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">c.892T>C</td><td headers="hd_h_mps3.T.notable_pathogenic_variants_in_ge_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Ser298Pro</td><td headers="hd_h_mps3.T.notable_pathogenic_variants_in_ge_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Homozygotes or compound heterozygotes w/attenuated MPS IIIA [<a class="bibr" href="#mps3.REF.meyer.2008.770" rid="mps3.REF.meyer.2008.770">Meyer et al 2008</a>]</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><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></dl><dl class="bkr_refwrap"><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/?report=reader">Quick Reference</a> for an explanation of nomenclature.</p></div></dd></dl><dl class="bkr_refwrap"><dt>1. </dt><dd><div id="mps3.TF.8.1"><p class="no_margin">Genes are listed alphabetically.</p></div></dd></dl><dl class="bkr_refwrap"><dt>2. </dt><dd><div id="mps3.TF.8.2"><p class="no_margin">Klüver-Bucy syndrome, a neurobehavioral phenotype that can be observed in MPS III</p></div></dd></dl><dl class="bkr_refwrap"><dt>3. </dt><dd><div id="mps3.TF.8.3"><p class="no_margin">See <a href="#mps3.GenotypePhenotype_Correlations">Genotype-Phenotype Correlations</a>.</p></div></dd></dl><dl class="bkr_refwrap"><dt>4. </dt><dd><div id="mps3.TF.8.4"><p class="no_margin">See <a href="#mps3.Prevalence">Prevalence</a>.</p></div></dd></dl></dl></div></div></div></article></div><div id="jr-scripts"><script src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/libs.min.js"> </script><script src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/jr.min.js"> </script><script type="text/javascript">if (typeof (jQuery) != 'undefined') { (function ($) { $(function () { var min = Math.ceil(1); var max = Math.floor(100000); var randomNum = Math.floor(Math.random() * (max - min)) + min; var surveyUrl = "/projects/Gene/portal/surveys/seqdbui-survey.js?rando=" + randomNum.toString(); $.getScript(surveyUrl, function () { try { ncbi.seqDbUISurvey.init(); } catch (err) { console.info(err); } }).fail(function (jqxhr, settings, exception) { console.info('Cannot load survey script', jqxhr); });; }); })(jQuery); };</script></div></div>
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