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<script type="text/javascript" src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/jr.boots.min.js"> </script><title>Multiple Sulfatase Deficiency - GeneReviews® - NCBI Bookshelf</title>
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<meta name="citation_inbook_title" content="GeneReviews® [Internet]">
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<meta name="citation_title" content="Multiple Sulfatase Deficiency">
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<meta name="citation_publisher" content="University of Washington, Seattle">
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<meta name="citation_date" content="2019/03/21">
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<meta name="citation_author" content="Lars Schlotawa">
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<meta name="citation_author" content="Laura Adang">
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<meta name="citation_author" content="Mauricio De Castro">
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<meta name="citation_author" content="Rebecca Ahrens-Nicklas">
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<meta name="citation_pmid" content="30896912">
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<meta name="citation_keywords" content="Formylglycine-generating enzyme">
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<meta name="citation_keywords" content="SUMF1">
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<meta name="citation_keywords" content="Multiple Sulfatase Deficiency">
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<meta name="DC.Title" content="Multiple Sulfatase Deficiency">
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<meta name="DC.Contributor" content="Lars Schlotawa">
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<meta name="DC.Contributor" content="Laura Adang">
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<meta name="DC.Contributor" content="Mauricio De Castro">
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<meta name="DC.Contributor" content="Rebecca Ahrens-Nicklas">
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<meta name="description" content="Initial symptoms of multiple sulfatase deficiency (MSD) can develop from infancy through early childhood, and presentation is widely variable. Some individuals display the multisystemic features characteristic of mucopolysaccharidosis disorders (e.g., developmental regression, organomegaly, skeletal deformities) while other individuals present primarily with neurologic regression (associated with leukodystrophy). Based on age of onset, rate of progression, and disease severity, several different clinical subtypes of MSD have been described:">
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<meta name="og:description" content="Initial symptoms of multiple sulfatase deficiency (MSD) can develop from infancy through early childhood, and presentation is widely variable. Some individuals display the multisystemic features characteristic of mucopolysaccharidosis disorders (e.g., developmental regression, organomegaly, skeletal deformities) while other individuals present primarily with neurologic regression (associated with leukodystrophy). Based on age of onset, rate of progression, and disease severity, several different clinical subtypes of MSD have been described:">
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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="_NBK538937_"><span class="title" itemprop="name">Multiple Sulfatase Deficiency</span></h1><p class="contribs">Schlotawa L, Adang L, De Castro M, et al.</p><p class="fm-aai"><a href="#_NBK538937_pubdet_">Publication Details</a></p><p><em>Estimated reading time: 25 minutes</em></p></div></div><div class="jig-ncbiinpagenav body-content whole_rhythm" data-jigconfig="allHeadingLevels: ['h2'],smoothScroll: false" itemprop="text"><div id="m-sulfatase-def.Summary" itemprop="description"><h2 id="_m-sulfatase-def_Summary_">Summary</h2><div><h4 class="inline">Clinical characteristics.</h4><p>Initial symptoms of multiple sulfatase deficiency (MSD) can develop from infancy through early childhood, and presentation is widely variable. Some individuals display the multisystemic features characteristic of mucopolysaccharidosis disorders (e.g., developmental regression, organomegaly, skeletal deformities) while other individuals present primarily with neurologic regression (associated with leukodystrophy). Based on age of onset, rate of progression, and disease severity, several different clinical subtypes of MSD have been described:</p><ul><li class="half_rhythm"><div>Neonatal MSD is the most severe with presentation in the prenatal period or at birth with rapid progression and death occurring within the first two years of life.</div></li><li class="half_rhythm"><div>Infantile MSD is the most common variant and may be characterized as attenuated (slower clinical course with cognitive disability and neurodegeneration identified in the 2nd year of life) or severe (loss of the majority of developmental milestones by age 5 years).</div></li><li class="half_rhythm"><div>Juvenile MSD is the rarest subtype with later onset of symptoms and subacute clinical presentation.</div></li></ul><p>Many of the features found in MSD are progressive, including neurologic deterioration, heart disease, hearing loss, and airway compromise.</p></div><div><h4 class="inline">Diagnosis/testing.</h4><p>The diagnosis of multiple sulfatase deficiency is established in a proband with low activity levels in at least two sulfatase enzymes and/or biallelic pathogenic variants in <i>SUMF1</i> identified by molecular genetic testing.</p></div><div><h4 class="inline">Management.</h4><p><i>Treatment of manifestations:</i> Progressive hydrocephalus, seizures, spasticity, spine instability or stenosis, eye anomalies, cardiovascular disease, hearing loss, poor growth, dental anomalies, developmental delays, and respiratory issues are managed in the standard fashion. Obstructive sleep apnea may be treated with adenoidectomy and/or tonsillectomy, although affected individuals have a higher surgical complication rate; ventilator support (CPAP, BiPAP) can also be considered. Precautions are needed during anesthesia to address airway maintenance, as progressive upper airway obstruction and cervical spine instability are common. Poor bone health may require supplementation with vitamin D and encouragement of weight-bearing exercises. Alternative routes for nutrition (tube feeding) are frequently necessary.</p><p><i>Surveillance:</i> Monitoring of head circumference at each visit; serial brain/spine imaging, as needed based on symptoms; cervical spine imaging prior to any procedure that requires neck extension. At least annual vitamin D level, eye examination with intraocular pressure measurement, EKG, echocardiogram, and audiology evaluation. Abdominal ultrasound, sleep study and pulmonary function tests, neuropsychiatric testing, and assessment of blood and urine acid-base balance as clinically indicated.</p><p><i>Agents/circumstances to avoid:</i> Neck hyperextension (including hyperextension used for intubation) because of the risk of spinal cord compression; foods that are a choking hazard.</p></div><div><h4 class="inline">Genetic Counseling.</h4><p>Multiple sulfatase deficiency is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% change of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Carrier testing for at-risk family members and prenatal testing for pregnancies at increased risk are possible using molecular genetic techniques if the pathogenic variants in the family are known.</p></div></div><div id="m-sulfatase-def.Diagnosis"><h2 id="_m-sulfatase-def_Diagnosis_">Diagnosis</h2><p>Formal clinical diagnostic criteria for multiple sulfatase deficiency have not been established.</p><div id="m-sulfatase-def.Suggestive_Findings"><h3>Suggestive Findings</h3><p>Multiple sulfatase deficiency <b>should be suspected</b> in individuals with the following clinical, laboratory, and imaging findings.</p><p>
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<b>Clinical findings</b>
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</p><ul><li class="half_rhythm"><div>Developmental delay with subsequent neurologic regression and psychomotor retardation</div></li><li class="half_rhythm"><div>Macrocephaly with or without hydrocephalus</div></li><li class="half_rhythm"><div>Epilepsy</div></li><li class="half_rhythm"><div>Poor growth with a progressive decrease in growth rate</div></li><li class="half_rhythm"><div>Coarse facial features</div></li><li class="half_rhythm"><div>Recurrent otitis media and/or upper respiratory tract infections</div></li><li class="half_rhythm"><div>Progressive hearing loss</div></li><li class="half_rhythm"><div>Hepatosplenomegaly</div></li><li class="half_rhythm"><div>Skeletal changes including kyphosis, gibbus deformity, hip dislocation, genu valgum</div></li><li class="half_rhythm"><div>Cardiac hypertrophy or thickening of cardiac valves</div></li><li class="half_rhythm"><div>Ichthyosis</div></li></ul><p>
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<b>Laboratory findings</b>
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</p><ul><li class="half_rhythm"><div class="half_rhythm">Decreased activity of at least two sulfatase enzymes on lysosomal enzyme testing analysis</div><div class="half_rhythm">Note: Individual enzyme activities may be higher than those seen in individuals with single enzyme deficiencies and some may be within normal ranges.</div></li><li class="half_rhythm"><div class="half_rhythm">Elevated urinary glycosaminoglycan levels</div></li><li class="half_rhythm"><div class="half_rhythm">Elevated urinary sulfatides</div></li></ul><p>
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<b>Imaging findings</b>
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</p><ul><li class="half_rhythm"><div>Abnormal brain MRI showing progressive demyelination, prominence of the perivascular spaces, cerebral volume loss, and/or hydrocephalus</div></li><li class="half_rhythm"><div>Skeletal radiographs demonstrating features of dysostosis multiplex including anomalies of the vertebrae, hands, feet, long bones, and skull</div></li></ul></div><div id="m-sulfatase-def.Establishing_the_Diagnos"><h3>Establishing the Diagnosis</h3><p>The diagnosis of multiple sulfatase deficiency <b>is established</b> in a proband with low activity levels in at least two sulfatase enzymes and/or biallelic pathogenic variants in <i>SUMF1</i> identified by molecular genetic testing (see <a href="/books/NBK538937/table/m-sulfatase-def.T.molecular_genetic_test/?report=objectonly" target="object" rid-ob="figobmsulfatasedefTmoleculargenetictest">Table 1</a>).</p><p>Molecular genetic testing approaches can include a combination of <b>gene-targeted testing</b> (single-gene testing or multigene panels) and <b>comprehensive</b>
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<b>genomic testing</b> (exome sequencing, exome array, genome sequencing) depending on the 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 multiple sulfatase deficiency is broad, individuals with the distinctive findings described in <a href="#m-sulfatase-def.Suggestive_Findings">Suggestive Findings</a> are likely to be diagnosed using gene-targeted testing (see <a href="#m-sulfatase-def.Option_1">Option 1</a>), whereas those in whom the diagnosis of multiple sulfatase deficiency has not been considered are more likely to be diagnosed using genomic testing (see <a href="#m-sulfatase-def.Option_2">Option 2</a>).</p><div id="m-sulfatase-def.Option_1"><h4>Option 1</h4><p>When the phenotypic and laboratory findings suggest the diagnosis of multiple sulfatase deficiency, molecular genetic testing approaches can include <b>single-gene testing</b> or use of a <b>multigene panel</b>:</p><ul><li class="half_rhythm"><div class="half_rhythm"><b>Single-gene testing.</b> Sequence analysis of <i>SUMF1</i> detects small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected.</div><div class="half_rhythm">Perform sequence analysis first. If only one or no pathogenic variant is found perform gene-targeted deletion/duplication analysis to detect intragenic deletions or duplications.</div></li><li class="half_rhythm"><div class="half_rhythm"><b>A multigene panel</b> that includes <i>SUMF1</i> and other genes of interest (see <a href="#m-sulfatase-def.Differential_Diagnosis">Differential Diagnosis</a>) is most likely to identify the genetic cause of the condition while limiting identification of variants of uncertain significance and pathogenic variants in unrelated genes. Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene may vary by laboratory. (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.</div><div class="half_rhythm">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>.</div></li></ul></div><div id="m-sulfatase-def.Option_2"><h4>Option 2</h4><p>When the diagnosis of multiple sulfatase deficiency is not considered because an individual has atypical phenotypic features, <b>comprehensive genomic testing</b> (which does not require the clinician to determine which gene[s] are likely involved) is the best option. <b>Exome sequencing</b> is the most commonly used genomic testing method; <b>genome sequencing</b> is also possible.</p><p><b>Exome array</b> (when clinically available) may be considered if exome sequencing is not diagnostic.</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="figmsulfatasedefTmoleculargenetictest"><a href="/books/NBK538937/table/m-sulfatase-def.T.molecular_genetic_test/?report=objectonly" target="object" title="Table 1. " class="img_link icnblk_img" rid-ob="figobmsulfatasedefTmoleculargenetictest"><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="m-sulfatase-def.T.molecular_genetic_test"><a href="/books/NBK538937/table/m-sulfatase-def.T.molecular_genetic_test/?report=objectonly" target="object" rid-ob="figobmsulfatasedefTmoleculargenetictest">Table 1. </a></h4><p class="float-caption no_bottom_margin">Molecular Genetic Testing Used in Multiple Sulfatase Deficiency </p></div></div></div></div></div><div id="m-sulfatase-def.Clinical_Characteristics"><h2 id="_m-sulfatase-def_Clinical_Characteristics_">Clinical Characteristics</h2><div id="m-sulfatase-def.Clinical_Description"><h3>Clinical Description</h3><p>Multiple sulfatase deficiency (MSD) is a multisystem lysosomal storage disorder with variable age of onset and wide variability in clinical presentation and rate of progression. Initial symptoms can present from infancy through early childhood [<a class="bibr" href="#m-sulfatase-def.REF.sabourdy.2015.31" rid="m-sulfatase-def.REF.sabourdy.2015.31">Sabourdy et al 2015</a>, <a class="bibr" href="#m-sulfatase-def.REF.ahrensnicklas.2018.337" rid="m-sulfatase-def.REF.ahrensnicklas.2018.337">Ahrens-Nicklas et al 2018</a>]. Many individuals experience global regression between age two and six years, approximately 12-60 months after symptom onset. Earlier onset of regression correlates with increased disease severity [<a class="bibr" href="#m-sulfatase-def.REF.sabourdy.2015.31" rid="m-sulfatase-def.REF.sabourdy.2015.31">Sabourdy et al 2015</a>]. Some individuals display the multisystemic features characteristic of mucopolysaccharidosis disorders, while others present primarily with neurologic regression (see <a href="#m-sulfatase-def.Pathophysiology">Pathophysiology</a>).</p><div id="m-sulfatase-def.Natural_History"><h4>Natural History</h4><p>Based on age of onset, rate of progression and disease severity, several different subtypes of MSD have been described [<a class="bibr" href="#m-sulfatase-def.REF.eto.1987.273" rid="m-sulfatase-def.REF.eto.1987.273">Eto et al 1987</a>]. The severity of the condition may correlate with the stability of the enzyme and residual enzyme activity (see <a href="#m-sulfatase-def.GenotypePhenotype_Correl">Genotype-Phenotype Correlations</a>). The subtypes are as follows.</p><p><b>Neonatal MSD</b> is the most severe form, in which affected Individuals typically have intrauterine growth restriction and respiratory distress at birth [<a class="bibr" href="#m-sulfatase-def.REF.busche.2009.969" rid="m-sulfatase-def.REF.busche.2009.969">Busche et al 2009</a>, <a class="bibr" href="#m-sulfatase-def.REF.garavelli.2014.86" rid="m-sulfatase-def.REF.garavelli.2014.86">Garavelli et al 2014</a>]. Dysmorphic features may include coarse facial features, thick eyebrows, hypoplastic nasal bone, bulbous nasal tip, posteriorly rotated ears, high arched palate, micrognathia, retrognathia, flared thorax, inverted nipples, and broad thumbs. Corneal clouding is frequently present. Disease progression is rapid and mortality is high, with death typically occurring within the first two years of life [<a class="bibr" href="#m-sulfatase-def.REF.burch.1986.409" rid="m-sulfatase-def.REF.burch.1986.409">Burch et al 1986</a>, <a class="bibr" href="#m-sulfatase-def.REF.busche.2009.969" rid="m-sulfatase-def.REF.busche.2009.969">Busche et al 2009</a>].</p><p><b>Infantile MSD,</b> the most common clinical presentation, is characterized by progressive neurodegeneration with loss of sensory and motor skills, similar to <a href="/books/n/gene/mld/?report=reader">arylsulfatase A deficiency</a> (metachromatic leukodystrophy). Typically, symptom onset is within the first three years of life. This phenotype may be further subdivided into attenuated (formally called "mild") and severe subtypes.</p><ul><li class="half_rhythm"><div><b>Attenuated infantile MSD</b> is characterized by a slower clinical course in which affected individuals are noted to have growth deficiency (1.5-3 SD below the mean), feeding difficulties, and developmental delay [<a class="bibr" href="#m-sulfatase-def.REF.ahrensnicklas.2018.337" rid="m-sulfatase-def.REF.ahrensnicklas.2018.337">Ahrens-Nicklas et al 2018</a>], with cognitive disability and neurodegeneration identified in the second year of life (range 3-36 months).</div><ul><li class="half_rhythm"><div>The ability to ambulate and communicate with a limited vocabulary may be preserved into late childhood (age 3-9 years), although by age nine most have significant impairments.</div></li><li class="half_rhythm"><div>Among eight individuals with infantile MSD, all demonstrated psychomotor retardation, hypotonia, and neurodegeneration, while 75% had ichthyosis and 25% had dysmorphic features [<a class="bibr" href="#m-sulfatase-def.REF.sabourdy.2015.31" rid="m-sulfatase-def.REF.sabourdy.2015.31">Sabourdy et al 2015</a>]. In a second series, nine individuals identified to have infantile MSD all demonstrated cognitive delay, neurodegeneration, and ichthyosis [<a class="bibr" href="#m-sulfatase-def.REF.schlotawa.2011.253" rid="m-sulfatase-def.REF.schlotawa.2011.253">Schlotawa et al 2011</a>].</div></li><li class="half_rhythm"><div>Dysmorphic features, if present, are subtle but may become more prominent with age.</div></li><li class="half_rhythm"><div>Prenatal manifestations, hepatosplenomegaly, and corneal clouding are rare [<a class="bibr" href="#m-sulfatase-def.REF.sabourdy.2015.31" rid="m-sulfatase-def.REF.sabourdy.2015.31">Sabourdy et al 2015</a>].</div></li></ul></li><li class="half_rhythm"><div><b>Severe</b>
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<b>infantile MSD</b> is characterized by a faster rate of disease progression and more extensive systemic involvement. Symptoms present within the first year of life and most individuals lose a majority of developmental milestones by age five years [<a class="bibr" href="#m-sulfatase-def.REF.sabourdy.2015.31" rid="m-sulfatase-def.REF.sabourdy.2015.31">Sabourdy et al 2015</a>, <a class="bibr" href="#m-sulfatase-def.REF.jaszczuk.2017.252" rid="m-sulfatase-def.REF.jaszczuk.2017.252">Jaszczuk et al 2017</a>].</div><ul><li class="half_rhythm"><div>Dysmorphic features, skeletal changes, and organomegaly are common [<a class="bibr" href="#m-sulfatase-def.REF.schlotawa.2011.253" rid="m-sulfatase-def.REF.schlotawa.2011.253">Schlotawa et al 2011</a>].</div></li><li class="half_rhythm"><div>Life span is significantly shortened, and many die within the first decade of life.</div></li></ul></li></ul><p><b>Juvenile MSD</b> is a rare subtype, although this could be influenced by ascertainment bias. It has a later onset with an attenuated clinical presentation. The diagnosis can sometimes be difficult to make owing to borderline residual sulfatase activity [<a class="bibr" href="#m-sulfatase-def.REF.church.2018.s32" rid="m-sulfatase-def.REF.church.2018.s32">Church et al 2018</a>]. Brain MRI findings are nonspecific and may include white matter signal abnormalities, corpus callosum thinning, and cerebellar atrophy.</p><ul><li class="half_rhythm"><div>Age of onset is between three and seven years with an insidious clinical presentation and neurologic decline.</div></li><li class="half_rhythm"><div>Presenting symptoms can include generalized tremor, hypotonia, and mild-moderate developmental delays [<a class="bibr" href="#m-sulfatase-def.REF.sabourdy.2015.31" rid="m-sulfatase-def.REF.sabourdy.2015.31">Sabourdy et al 2015</a>].</div></li><li class="half_rhythm"><div>Affected individuals can also develop ichthyosis, visual loss (although corneal clouding is rare), and behavioral abnormalities, and may have minor dysmorphic features (broad thumbs and index fingers) that frequently become more prominent with age [<a class="bibr" href="#m-sulfatase-def.REF.blancoaguirre.2001.388" rid="m-sulfatase-def.REF.blancoaguirre.2001.388">Blanco-Aguirre et al 2001</a>].</div></li><li class="half_rhythm"><div>The oldest known person with the condition survived until the fourth decade of life [Author, personal communication].</div></li><li class="half_rhythm"><div>Individuals with juvenile MSD can retain the ability to walk into their teenage years.</div></li></ul></div><div id="m-sulfatase-def.Clinical_Features_Common"><h4>Clinical Features Common To All Subtypes</h4><p>Many of the features found in MSD can be progressive, including the neurologic deterioration, heart disease, hearing loss, and airway compromise. The progressive nature of the disease is at least in part due to the accumulation of glycosaminoglycans (GAGs) and other substrates, including sulfatides.</p><p><b>Neurologic</b> features include:</p><ul><li class="half_rhythm"><div>Developmental delay and progressive neurologic deterioration, including long track signs (spasticity)</div></li><li class="half_rhythm"><div>Ataxia</div></li><li class="half_rhythm"><div>Autistic features</div></li><li class="half_rhythm"><div>Epilepsy [<a class="bibr" href="#m-sulfatase-def.REF.incecik.2017.779" rid="m-sulfatase-def.REF.incecik.2017.779">Incecik & Herguner 2017</a>]</div></li><li class="half_rhythm"><div>Microcephaly [<a class="bibr" href="#m-sulfatase-def.REF.miskin.2016.98" rid="m-sulfatase-def.REF.miskin.2016.98">Miskin et al 2016</a>] or macrocephaly; hydrocephalus has been reported [<a class="bibr" href="#m-sulfatase-def.REF.incecik.2017.779" rid="m-sulfatase-def.REF.incecik.2017.779">Incecik & Herguner 2017</a>].</div></li></ul><p><b>Musculoskeletal</b> features:</p><ul><li class="half_rhythm"><div>Short stature</div></li><li class="half_rhythm"><div>Irregular ribs (typically paddle-shaped with widening anteriorly and tapering posteriorly) associated with dysostosis multiplex</div></li><li class="half_rhythm"><div>Scoliosis and/or kyphosis</div></li><li class="half_rhythm"><div>Vertebral abnormalities, including odontoid dysplasia, atlanto-axial instability, cervical spinal canal stenosis, and vertebral body abnormalities (wedge-shaped vertebral bodies, anterior beaking with posterior scalloping, and platyspondyly)</div></li><li class="half_rhythm"><div>Vertebral instability and risk of spinal cord compression, which can be dangerous with neck hyperextension (such as occurs during intubation)</div></li><li class="half_rhythm"><div>Short metacarpals</div></li><li class="half_rhythm"><div>Joint stiffness and contractures, which may pose a prominent issue that can impede mobility [<a class="bibr" href="#m-sulfatase-def.REF.burk.1984.574" rid="m-sulfatase-def.REF.burk.1984.574">Burk et al 1984</a>]</div></li><li class="half_rhythm"><div>Broad thumbs and toes [<a class="bibr" href="#m-sulfatase-def.REF.santos.2006.955" rid="m-sulfatase-def.REF.santos.2006.955">Santos & Hoo 2006</a>]</div></li></ul><p><b>Growth restriction</b> may be of prenatal onset, particularly in the neonatal form [<a class="bibr" href="#m-sulfatase-def.REF.incecik.2013.720" rid="m-sulfatase-def.REF.incecik.2013.720">Incecik et al 2013</a>, <a class="bibr" href="#m-sulfatase-def.REF.sabourdy.2015.31" rid="m-sulfatase-def.REF.sabourdy.2015.31">Sabourdy et al 2015</a>].</p><p><b>Ophthalmologic</b> features:</p><ul><li class="half_rhythm"><div>Glaucoma</div></li><li class="half_rhythm"><div>Strabismus</div></li><li class="half_rhythm"><div>Retinal degeneration</div></li><li class="half_rhythm"><div>Corneal clouding</div></li><li class="half_rhythm"><div>Cataracts</div></li><li class="half_rhythm"><div>Retinitis pigmentosa [<a class="bibr" href="#m-sulfatase-def.REF.sabourdy.2015.31" rid="m-sulfatase-def.REF.sabourdy.2015.31">Sabourdy et al 2015</a>]</div></li><li class="half_rhythm"><div>Myopia</div></li></ul><p><b>Cardiovascular</b>
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<b>manifestations</b> may include atrial septal defects [<a class="bibr" href="#m-sulfatase-def.REF.incecik.2013.720" rid="m-sulfatase-def.REF.incecik.2013.720">Incecik et al 2013</a>] and aortic insufficiency [<a class="bibr" href="#m-sulfatase-def.REF.guerra.1990.406" rid="m-sulfatase-def.REF.guerra.1990.406">Guerra et al 1990</a>]. Individuals with MSD are at risk of developing cardiac manifestations similar to those seen in other lysosomal storage disorders: secondary valve disease, cardiac hypertrophy, coronary artery disease, arrhythmias, and hypertension [<a class="bibr" href="#m-sulfatase-def.REF.braunlin.2011.1183" rid="m-sulfatase-def.REF.braunlin.2011.1183">Braunlin et al 2011</a>, <a class="bibr" href="#m-sulfatase-def.REF.sabourdy.2015.31" rid="m-sulfatase-def.REF.sabourdy.2015.31">Sabourdy et al 2015</a>, <a class="bibr" href="#m-sulfatase-def.REF.jaszczuk.2017.252" rid="m-sulfatase-def.REF.jaszczuk.2017.252">Jaszczuk et al 2017</a>].</p><p><b>Ear, nose, and throat.</b> Progressive conductive and/or sensorineural hearing loss and recurrent otitis media are common [<a class="bibr" href="#m-sulfatase-def.REF.sabourdy.2015.31" rid="m-sulfatase-def.REF.sabourdy.2015.31">Sabourdy et al 2015</a>].</p><p><b>Skin.</b> Ichthyosis (dry, scaly skin) and hypertrichosis are common [<a class="bibr" href="#m-sulfatase-def.REF.incecik.2013.720" rid="m-sulfatase-def.REF.incecik.2013.720">Incecik et al 2013</a>].</p><p><b>Dental</b>
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<b>abnormalities</b> can be detected early in life and are progressive. They can include thin enamel of deciduous and permanent teeth, dark discoloration of dentin, malocclusion, and anterior open bite [<a class="bibr" href="#m-sulfatase-def.REF.zilberman.2016.95" rid="m-sulfatase-def.REF.zilberman.2016.95">Zilberman & Bibi 2016</a>].</p><p><b>Gastrointestinal system.</b> Many affected individuals develop hepatosplenomegaly, which is possibly secondary to GAG accumulation. Swallowing dysfunction may lead to sialorrhea and feeding difficulties. Many individuals require feeding tubes to safely and efficiently meet their caloric needs.</p><p><b>Respiratory.</b> Individuals are at risk of progressive upper airway obstruction. Many individuals experience both central and peripheral sleep apnea. Individuals are also at risk for aspiration pneumonia.</p><p><b>Metabolic acidosis.</b> Loss of arylsulfatase A (ARSA) activity has been associated with renal dysfunction and increased predisposition to metabolic acidosis [<a class="bibr" href="#m-sulfatase-def.REF.lorioli.2015.48" rid="m-sulfatase-def.REF.lorioli.2015.48">Lorioli et al 2015</a>]. The true risk in MSD is not currently known, but given that most affected individuals have decreased ARSA activity, this should be considered.</p><p><b>Brain MRI features.</b> The most common findings are white matter (periventricular) abnormalities with U fiber sparing, radiating stripes, and severe white matter atrophy [<a class="bibr" href="#m-sulfatase-def.REF.prasad.2014.626" rid="m-sulfatase-def.REF.prasad.2014.626">Prasad et al 2014</a>]. Other abnormal imaging findings include [<a class="bibr" href="#m-sulfatase-def.REF.van_der_knaap.2013" rid="m-sulfatase-def.REF.van_der_knaap.2013">van der Knaap & Valk 2013</a>, <a class="bibr" href="#m-sulfatase-def.REF.sabourdy.2015.31" rid="m-sulfatase-def.REF.sabourdy.2015.31">Sabourdy et al 2015</a>, <a class="bibr" href="#m-sulfatase-def.REF.ahrensnicklas.2018.337" rid="m-sulfatase-def.REF.ahrensnicklas.2018.337">Ahrens-Nicklas et al 2018</a>]:</p><ul><li class="half_rhythm"><div>Cerebral atrophy and/or cerebellar atrophy</div></li><li class="half_rhythm"><div>Abnormalities of the corpus callosum</div></li><li class="half_rhythm"><div>Dilatation of the ventricular system</div></li><li class="half_rhythm"><div>Prominence of the sulci</div></li><li class="half_rhythm"><div>Enlarged perivascular spaces</div></li><li class="half_rhythm"><div>Cervical cord compression</div></li><li class="half_rhythm"><div>Delayed myelination</div></li></ul></div></div><div id="m-sulfatase-def.Pathophysiology"><h3>Pathophysiology</h3><p>The wide clinical spectrum seen in MSD is largely a function of the unique pathophysiology of this condition, as multiple pathways are affected by a common enzymatic defect. All known 17 human sulfatases may be affected; thus, the clinical presentation is a composite of the effects of each individual sulfatase deficiency [<a class="bibr" href="#m-sulfatase-def.REF.hopwood.2001" rid="m-sulfatase-def.REF.hopwood.2001">Hopwood & Ballabio 2001</a>]. Of these sulfatases, nine have each been implicated in distinct human diseases (albeit with overlapping features) [<a class="bibr" href="#m-sulfatase-def.REF.dierks.2009.710" rid="m-sulfatase-def.REF.dierks.2009.710">Dierks et al 2009</a>, <a class="bibr" href="#m-sulfatase-def.REF.khateb.2018.1004" rid="m-sulfatase-def.REF.khateb.2018.1004">Khateb et al 2018</a>]. The clinical presentation is a combination of these nine enzymatic defects, with affected individuals having signs and symptoms of <a href="/books/n/gene/mld/?report=reader">arylsulfatase A deficiency</a> (metachromatic leukodystrophy), Maroteaux-Lamy syndrome, X-linked ichthyosis, <a href="/books/n/gene/hunter/?report=reader">mucopolysaccharidosis type II</a> (Hunter syndrome), mucopolysaccharidosis type IIIA (Sanfilippo A syndrome), and <a href="/books/n/gene/mps4a/?report=reader">mucopolysaccharidosis type IVA</a> (Morquio syndrome). The contribution to clinical phenotype from the sulfatases without a clinically defined phenotype is unknown.</p></div><div id="m-sulfatase-def.GenotypePhenotype_Correl"><h3>Genotype-Phenotype Correlations</h3><p>Sulfatase-modifying-factor-1 (SUMF1) protein stability and residual formylglycine-generating enzyme (FGE) activity influence the clinical presentation in individuals with pathogenic changes in <i>SUMF1</i>. Individuals with unstable SUMF1 protein and low residual FGE activity display a severe late-infantile onset phenotype with rapid progression of MSD and neurologic deterioration. Individuals with higher levels of residual FGE enzyme activity often have attenuated forms of MSD with fewer symptoms, slower disease progression, and later onset of regression. Biallelic nonsense variants and deletions have been reported and are associated with a severe neonatal presentation [<a class="bibr" href="#m-sulfatase-def.REF.schlotawa.2008.205" rid="m-sulfatase-def.REF.schlotawa.2008.205">Schlotawa et al 2008</a>, <a class="bibr" href="#m-sulfatase-def.REF.schlotawa.2013" rid="m-sulfatase-def.REF.schlotawa.2013">Schlotawa et al 2013</a>, <a class="bibr" href="#m-sulfatase-def.REF.sabourdy.2015.31" rid="m-sulfatase-def.REF.sabourdy.2015.31">Sabourdy et al 2015</a>].</p><p>For a small subset of pathogenic missense variants, experimental evidence for residual SUMF1 activity and FGE stability has been published and specific genotype-phenotype correlations exist.</p><ul><li class="half_rhythm"><div>Homozygosity for the p.Gly263Val or p.Ala279Val <i>SUMF1</i> alleles is associated with attenuated late-infantile MSD.</div></li><li class="half_rhythm"><div>Homozygosity for the p.Ser155Pro, p.Gly247Arg, or p.Arg349Trp <i>SUMF1</i> alleles is associated with severe late-infantile MSD [<a class="bibr" href="#m-sulfatase-def.REF.cosma.2004.576" rid="m-sulfatase-def.REF.cosma.2004.576">Cosma et al 2004</a>, <a class="bibr" href="#m-sulfatase-def.REF.schlotawa.2008.205" rid="m-sulfatase-def.REF.schlotawa.2008.205">Schlotawa et al 2008</a>, <a class="bibr" href="#m-sulfatase-def.REF.schlotawa.2011.253" rid="m-sulfatase-def.REF.schlotawa.2011.253">Schlotawa et al 2011</a>, <a class="bibr" href="#m-sulfatase-def.REF.schlotawa.2013" rid="m-sulfatase-def.REF.schlotawa.2013">Schlotawa et al 2013</a>].</div></li></ul><p>Non-experimental prediction methods attempting to correlate a particular <i>SUMF1</i> variant with FGE stability and clinical phenotype are not exact. There is no reliable genotype-phenotype correlation possible for affected individuals with compound heterozygous pathogenic missense variants. Finally, laboratory parameters, especially single sulfatase activity, GAG, and sulfatide levels, do not correlate well with the clinical presentation and can be normal in some cases [<a class="bibr" href="#m-sulfatase-def.REF.sabourdy.2015.31" rid="m-sulfatase-def.REF.sabourdy.2015.31">Sabourdy et al 2015</a>, <a class="bibr" href="#m-sulfatase-def.REF.ahrensnicklas.2018.337" rid="m-sulfatase-def.REF.ahrensnicklas.2018.337">Ahrens-Nicklas et al 2018</a>].</p></div><div id="m-sulfatase-def.Nomenclature"><h3>Nomenclature</h3><p>Other terms used to describe MSD are Austin disease (named after Dr James Austin, who first described the condition [<a class="bibr" href="#m-sulfatase-def.REF.austin.1964.15c" rid="m-sulfatase-def.REF.austin.1964.15c">Austin et al 1964</a>]), juvenile sulfatidosis, and mucosulfatidosis.</p></div><div id="m-sulfatase-def.Prevalence"><h3>Prevalence</h3><p>The estimated prevalence of MSD is one in 1.4 million individuals. There have been approximately 75-100 cases reported to date [<a class="bibr" href="#m-sulfatase-def.REF.hopwood.2001" rid="m-sulfatase-def.REF.hopwood.2001">Hopwood & Ballabio 2001</a>, <a class="bibr" href="#m-sulfatase-def.REF.ahrensnicklas.2018.337" rid="m-sulfatase-def.REF.ahrensnicklas.2018.337">Ahrens-Nicklas et al 2018</a>], with approximately 50 living affected individuals identified through support and advocacy groups. MSD has been reported in individuals of all ethnicities throughout the world [<a class="bibr" href="#m-sulfatase-def.REF.artigal_s.2009.493" rid="m-sulfatase-def.REF.artigal_s.2009.493">Artigalás et al 2009</a>, <a class="bibr" href="#m-sulfatase-def.REF.incecik.2013.720" rid="m-sulfatase-def.REF.incecik.2013.720">Incecik et al 2013</a>, <a class="bibr" href="#m-sulfatase-def.REF.meng.2013.836" rid="m-sulfatase-def.REF.meng.2013.836">Meng et al 2013</a>, <a class="bibr" href="#m-sulfatase-def.REF.garavelli.2014.86" rid="m-sulfatase-def.REF.garavelli.2014.86">Garavelli et al 2014</a>]. It is likely that this condition is underrecognized and underdiagnosed, particularly in areas of the world where access to advanced molecular genetic testing is not readily available.</p></div></div><div id="m-sulfatase-def.Genetically_Related_Alle"><h2 id="_m-sulfatase-def_Genetically_Related_Alle_">Genetically Related (Allelic) Disorders</h2><p>No phenotypes other than those discussed in this <i>GeneReview</i> are known to be associated with germline pathogenic variants in <i>SUMF1</i>.</p></div><div id="m-sulfatase-def.Differential_Diagnosis"><h2 id="_m-sulfatase-def_Differential_Diagnosis_">Differential Diagnosis</h2><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figmsulfatasedefTdisorderstoconsider"><a href="/books/NBK538937/table/m-sulfatase-def.T.disorders_to_consider/?report=objectonly" target="object" title="Table 2. " class="img_link icnblk_img" rid-ob="figobmsulfatasedefTdisorderstoconsider"><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="m-sulfatase-def.T.disorders_to_consider"><a href="/books/NBK538937/table/m-sulfatase-def.T.disorders_to_consider/?report=objectonly" target="object" rid-ob="figobmsulfatasedefTdisorderstoconsider">Table 2. </a></h4><p class="float-caption no_bottom_margin">Disorders to Consider in the Differential Diagnosis of Multiple Sulfatase Deficiency (MSD) </p></div></div></div><div id="m-sulfatase-def.Management"><h2 id="_m-sulfatase-def_Management_">Management</h2><div id="m-sulfatase-def.Evaluations_Following_In"><h3>Evaluations Following Initial Diagnosis</h3><p>To establish the extent of disease and needs in an individual diagnosed with multiple sulfatase deficiency, the evaluations summarized in <a href="/books/NBK538937/table/m-sulfatase-def.T.recommended_evaluation/?report=objectonly" target="object" rid-ob="figobmsulfatasedefTrecommendedevaluation">Table 3</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="figmsulfatasedefTrecommendedevaluation"><a href="/books/NBK538937/table/m-sulfatase-def.T.recommended_evaluation/?report=objectonly" target="object" title="Table 3. " class="img_link icnblk_img" rid-ob="figobmsulfatasedefTrecommendedevaluation"><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="m-sulfatase-def.T.recommended_evaluation"><a href="/books/NBK538937/table/m-sulfatase-def.T.recommended_evaluation/?report=objectonly" target="object" rid-ob="figobmsulfatasedefTrecommendedevaluation">Table 3. </a></h4><p class="float-caption no_bottom_margin">Recommended Evaluations Following Initial Diagnosis in Individuals with Multiple Sulfatase Deficiency </p></div></div></div><div id="m-sulfatase-def.Treatment_of_Manifestati"><h3>Treatment of Manifestations</h3><p>A detailed clinical management guide was recently published delineating a symptomatic management strategy [<a class="bibr" href="#m-sulfatase-def.REF.ahrensnicklas.2018.337" rid="m-sulfatase-def.REF.ahrensnicklas.2018.337">Ahrens-Nicklas et al 2018</a>] (<a href="https://www.sciencedirect.com/science/article/pii/S109671921730759X" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">full text</a>).</p><p>While there are no targeted therapeutic options to date, many complications are amenable to symptomatic management [<a class="bibr" href="#m-sulfatase-def.REF.adang.2017.18" rid="m-sulfatase-def.REF.adang.2017.18">Adang et al 2017</a>]. An individualized care plan can be designed by the primary and specialist providers. In addition to the primary care provider, the care team will often include neurologists, metabolic geneticists with genetic counselors, gastroenterologists, ophthalmologists, cardiologists, and physiatrists. Additional care providers may include speech therapists, occupational therapists, physical therapists, nutritionists, and dentists. Special efforts should be made to maintain mobility and social communication skills until such skills are lost.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figmsulfatasedefTtreatmentofmanifesta"><a href="/books/NBK538937/table/m-sulfatase-def.T.treatment_of_manifesta/?report=objectonly" target="object" title="Table 4. " class="img_link icnblk_img" rid-ob="figobmsulfatasedefTtreatmentofmanifesta"><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="m-sulfatase-def.T.treatment_of_manifesta"><a href="/books/NBK538937/table/m-sulfatase-def.T.treatment_of_manifesta/?report=objectonly" target="object" rid-ob="figobmsulfatasedefTtreatmentofmanifesta">Table 4. </a></h4><p class="float-caption no_bottom_margin">Treatment of Manifestations in Individuals with Multiple Sulfatase Deficiency </p></div></div></div><div id="m-sulfatase-def.Surveillance"><h3>Surveillance</h3><p>No definitive surveillance guidelines have been established, although particular attention to and monitoring of the cardiac, respiratory, ophthalmologic, neurologic, skeletal, and gastroenterologic systems is indicated [<a class="bibr" href="#m-sulfatase-def.REF.ahrensnicklas.2018.337" rid="m-sulfatase-def.REF.ahrensnicklas.2018.337">Ahrens-Nicklas et al 2018</a>].</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figmsulfatasedefTsurveillancetoconsid"><a href="/books/NBK538937/table/m-sulfatase-def.T.surveillance_to_consid/?report=objectonly" target="object" title="Table 5. " class="img_link icnblk_img" rid-ob="figobmsulfatasedefTsurveillancetoconsid"><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="m-sulfatase-def.T.surveillance_to_consid"><a href="/books/NBK538937/table/m-sulfatase-def.T.surveillance_to_consid/?report=objectonly" target="object" rid-ob="figobmsulfatasedefTsurveillancetoconsid">Table 5. </a></h4><p class="float-caption no_bottom_margin">Surveillance to Consider for Individuals with Multiple Sulfatase Deficiency </p></div></div></div><div id="m-sulfatase-def.AgentsCircumstances_to_A"><h3>Agents/Circumstances to Avoid</h3><p>Individuals should avoid neck hyperextension, including hyperextension used for intubation, because of the risk of spinal cord compression. Foods that are choking hazards should also be avoided.</p></div><div id="m-sulfatase-def.Evaluation_of_Relatives"><h3>Evaluation of Relatives at Risk</h3><p>See <a href="#m-sulfatase-def.Related_Genetic_Counseli">Genetic Counseling</a> for issues related to testing of at-risk relatives for genetic counseling purposes.</p></div><div id="m-sulfatase-def.Therapies_Under_Investig"><h3>Therapies Under Investigation</h3><p>A multi-institutional natural history study is underway through the Myelin Disorders Biorepository Project (Clinical Trials Identifier: <a href="https://clinicaltrials.gov/show/NCT03047369" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NCT03047369</a>).</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="m-sulfatase-def.Genetic_Counseling"><h2 id="_m-sulfatase-def_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="m-sulfatase-def.Mode_of_Inheritance"><h3>Mode of Inheritance</h3><p>Multiple sulfatase deficiency is inherited in an autosomal recessive manner.</p></div><div id="m-sulfatase-def.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>SUMF1</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> To date, individuals with multiple sulfatase deficiency are not known to reproduce.</p><p><b>Other family members.</b> Each sib of the proband's parents is at a 50% risk of being a carrier of a <i>SUMF1</i> pathogenic variant.</p></div><div id="m-sulfatase-def.Carrier_Heterozygote_Det"><h3>Carrier (Heterozygote) Detection</h3><p>Carrier testing for at-risk relatives requires prior identification of the <i>SUMF1</i> pathogenic variants in the family.</p></div><div id="m-sulfatase-def.Related_Genetic_Counseli"><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 carriers or are at risk of being carriers.</div></li></ul><p><b>DNA banking.</b> Because it is likely that testing methodology and our understanding of genes, pathogenic mechanisms, and diseases will improve in the future, consideration should be given to banking DNA from probands in whom a molecular diagnosis has not been confirmed (i.e., the causative pathogenic mechanism is unknown). For more information, see <a class="bibr" href="#m-sulfatase-def.REF.huang.2022.389" rid="m-sulfatase-def.REF.huang.2022.389">Huang et al [2022]</a>.</p></div><div id="m-sulfatase-def.Prenatal_Testing_and_Pre"><h3>Prenatal Testing and Preimplantation Genetic Testing</h3><p>Once the <i>SUMF1</i> pathogenic variants have been identified in an affected family member, prenatal 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, particularly if the testing is being considered for the purpose of pregnancy termination rather than early diagnosis. 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="m-sulfatase-def.Resources"><h2 id="_m-sulfatase-def_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>MSD Action Foundation</b>
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</div><div>Grattan Lodge</div><div> Dublin </div><div>Ireland</div><div><b>Email:</b> alanfinglas@gmail.com; info@msdactionfoundation.org</div><div>
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<a href="http://www.MSDactionFoundation.org" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">www.MSDactionFoundation.org</a>
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</div></li><li class="half_rhythm"><div>
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<b>United MSD Foundation</b>
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</div><div><b>Phone:</b> 228-295-7084</div><div>
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<a href="http://curemsd.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">www.curemsd.org</a>
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</div></li><li class="half_rhythm"><div>
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<b>Metabolic Support UK</b>
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</div><div>United Kingdom</div><div><b>Phone:</b> 0845 241 2173</div><div>
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<a href="https://metabolicsupportuk.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">metabolicsupportuk.org</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></ul>
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</div><div id="m-sulfatase-def.Molecular_Genetics"><h2 id="_m-sulfatase-def_Molecular_Genetics_">Molecular Genetics</h2><p><i>Information in the Molecular Genetics and OMIM tables may differ from that elsewhere in the GeneReview: tables may contain more recent information. —</i>ED.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figmsulfatasedefmolgenTA"><a href="/books/NBK538937/table/m-sulfatase-def.molgen.TA/?report=objectonly" target="object" title="Table A." class="img_link icnblk_img" rid-ob="figobmsulfatasedefmolgenTA"><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="m-sulfatase-def.molgen.TA"><a href="/books/NBK538937/table/m-sulfatase-def.molgen.TA/?report=objectonly" target="object" rid-ob="figobmsulfatasedefmolgenTA">Table A.</a></h4><p class="float-caption no_bottom_margin">Multiple Sulfatase Deficiency: Genes and Databases </p></div></div><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figmsulfatasedefmolgenTB"><a href="/books/NBK538937/table/m-sulfatase-def.molgen.TB/?report=objectonly" target="object" title="Table B." class="img_link icnblk_img" rid-ob="figobmsulfatasedefmolgenTB"><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="m-sulfatase-def.molgen.TB"><a href="/books/NBK538937/table/m-sulfatase-def.molgen.TB/?report=objectonly" target="object" rid-ob="figobmsulfatasedefmolgenTB">Table B.</a></h4><p class="float-caption no_bottom_margin">OMIM Entries for Multiple Sulfatase Deficiency (View All in OMIM) </p></div></div><div id="m-sulfatase-def.Molecular_Pathogenesis"><h3>Molecular Pathogenesis</h3><p>Multiple sulfatase deficiency (MSD) is the result of a defect of the post-translational modification of cellular sulfatases. Sulfatases are a group of enzymes necessary for the breakdown of sulfate residues on macromolecules in cells (e.g., sulfatides, glycosaminoglycans, transcription factors). All newly synthesized sulfatases require activation by formylglycine-generating enzyme (FGE), encoded by <i>SUMF1</i>, for full catalytic activity. As the majority of cellular sulfatases are located in the lysosome, sulfatase dysfunction induces lysosomal storage of several substrates and cellular pathology (e.g., blockade of autophagy) leading to the symptoms that individuals with MSD experience [<a class="bibr" href="#m-sulfatase-def.REF.dierks.2003.435" rid="m-sulfatase-def.REF.dierks.2003.435">Dierks et al 2003</a>, <a class="bibr" href="#m-sulfatase-def.REF.cosma.2004.576" rid="m-sulfatase-def.REF.cosma.2004.576">Cosma et al 2004</a>, <a class="bibr" href="#m-sulfatase-def.REF.dierks.2005.541" rid="m-sulfatase-def.REF.dierks.2005.541">Dierks et al 2005</a>, <a class="bibr" href="#m-sulfatase-def.REF.sardiello.2005.3203" rid="m-sulfatase-def.REF.sardiello.2005.3203">Sardiello et al 2005</a>, <a class="bibr" href="#m-sulfatase-def.REF.settembre.2008.119" rid="m-sulfatase-def.REF.settembre.2008.119">Settembre et al 2008</a>]).</p><p><b>Gene structure.</b>
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<i>SUMF1</i> encodes a 2,152-bp transcript that contains nine exons. Eight alternatively spliced transcripts – encoding five protein isoforms with unknown clinical significance – have been predicted.</p><p>See <a href="/books/NBK538937/?report=reader#m-sulfatase-def.molgen.TA">Table A</a>, <b>Gene</b> for a detailed summary of gene and protein information.</p><p><b>Pathogenic variants.</b> More than 50 pathogenic <i>SUMF1</i> variants have been reported. Variant types include missense variants, insertions and deletions, and splicing and nonsense variants. Large copy number changes have also been reported. The most frequently observed MSD-causing variants are p.Gly247Arg, p.Ser155Pro, p.Arg349Trp, p.Ala279Val, p.Arg345Cys, and p.Gly263Val. Abundant hot spots for missense loss-of-function variants are p.Asn259 (variants p.Asn259Ile,Lys,Ser) and p.Arg349 (variants p.Arg349Gly,Glu,Trp). 31% of all variants are private [Authors, unpublished data].</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figmsulfatasedefTsumf1pathogenicvaria"><a href="/books/NBK538937/table/m-sulfatase-def.T.sumf1_pathogenic_varia/?report=objectonly" target="object" title="Table 6. " class="img_link icnblk_img" rid-ob="figobmsulfatasedefTsumf1pathogenicvaria"><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="m-sulfatase-def.T.sumf1_pathogenic_varia"><a href="/books/NBK538937/table/m-sulfatase-def.T.sumf1_pathogenic_varia/?report=objectonly" target="object" rid-ob="figobmsulfatasedefTsumf1pathogenicvaria">Table 6. </a></h4><p class="float-caption no_bottom_margin"><i>SUMF1</i> Pathogenic Variants Discussed in This <i>GeneReview</i> </p></div></div><p><b>Normal gene product.</b>
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<i>SUMF1</i> encodes the sulfatase-modifying-factor-1 protein, alternatively named formylglycine-generating enzyme (FGE), a 374-amino acid protein. FGE contains a single core domain with an N-terminal extension (amino acids 34-72) and a low amount of secondary structure. It is stabilized by two cysteine interactions. Four additional cysteine residues are involved in the enzyme's catalytic function with p.Cys336 and p.Cys341 forming the active site of FGE.</p><p>FGE recognizes newly synthesized sulfatases via an amino acid motif (CXPSR) that is present in all sulfatases. FGE oxidizes the cysteine to an aldehyde, C-alpha-formylglycine,which is indispensable for sulfatase catalytic function [<a class="bibr" href="#m-sulfatase-def.REF.dierks.2005.541" rid="m-sulfatase-def.REF.dierks.2005.541">Dierks et al 2005</a>, <a class="bibr" href="#m-sulfatase-def.REF.sardiello.2005.3203" rid="m-sulfatase-def.REF.sardiello.2005.3203">Sardiello et al 2005</a>].</p><p><b>Abnormal gene product.</b> MSD occurs though a loss-of-function mechanism as evidenced by missense variants reducing protein stability and enzymatic activity. The majority of disease-associated missense variants result in an unstable FGE protein with a reduced half-life and reduced enzymatic activity.</p><p>A minority of FGE protein pathogenic variants alter regulation by the ER quality-control process, protein-disulfide-isomerase (PDI). These variants result in an abnormal arrangement of intramolecular stabilizing disulfide bridges; PDI recognizes the misfolded FGE and induces early degradation [<a class="bibr" href="#m-sulfatase-def.REF.dierks.2005.541" rid="m-sulfatase-def.REF.dierks.2005.541">Dierks et al 2005</a>, <a class="bibr" href="#m-sulfatase-def.REF.schlotawa.2008.205" rid="m-sulfatase-def.REF.schlotawa.2008.205">Schlotawa et al 2008</a>, <a class="bibr" href="#m-sulfatase-def.REF.schlotawa.2011.253" rid="m-sulfatase-def.REF.schlotawa.2011.253">Schlotawa et al 2011</a>, <a class="bibr" href="#m-sulfatase-def.REF.schlotawa.2013" rid="m-sulfatase-def.REF.schlotawa.2013">Schlotawa et al 2013</a>, <a class="bibr" href="#m-sulfatase-def.REF.meshach_paul.2018.3575" rid="m-sulfatase-def.REF.meshach_paul.2018.3575">Meshach Paul et al 2018</a>, <a class="bibr" href="#m-sulfatase-def.REF.schlotawa.2018.27" rid="m-sulfatase-def.REF.schlotawa.2018.27">Schlotawa et al 2018</a>].</p><p>Both the <i>SUMF1</i> and sulfatase genes and protein structures are highly evolutionarily conserved. No alternative sulfatase activation mechanism exists in eukaryotes. FGE is predominantly localized to the endoplasmic reticulum but is also secreted. The function of secreted FGE is unknown. Known interacting partners are redox proteins in the ER (e.g., PDI and ERp44) and its nonfunctional homolog SUMF2 (pFGE) [<a class="bibr" href="#m-sulfatase-def.REF.landgrebe.2003.47" rid="m-sulfatase-def.REF.landgrebe.2003.47">Landgrebe et al 2003</a>, <a class="bibr" href="#m-sulfatase-def.REF.preusserkunze.2005.14900" rid="m-sulfatase-def.REF.preusserkunze.2005.14900">Preusser-Kunze et al 2005</a>, <a class="bibr" href="#m-sulfatase-def.REF.fraldi.2008.2610" rid="m-sulfatase-def.REF.fraldi.2008.2610">Fraldi et al 2008</a>, <a class="bibr" href="#m-sulfatase-def.REF.mariappan.2008a.11556" rid="m-sulfatase-def.REF.mariappan.2008a.11556">Mariappan et al 2008a</a>, <a class="bibr" href="#m-sulfatase-def.REF.mariappan.2008b.6375" rid="m-sulfatase-def.REF.mariappan.2008b.6375">Mariappan et al 2008b</a>].</p></div></div><div id="m-sulfatase-def.Chapter_Notes"><h2 id="_m-sulfatase-def_Chapter_Notes_">Chapter Notes</h2><div id="m-sulfatase-def.Revision_History"><h3>Revision History</h3><ul><li class="half_rhythm"><div>21 March 2019 (ma) Review posted live</div></li><li class="half_rhythm"><div>27 August 2018 (ran) Original submission</div></li></ul></div></div><div id="m-sulfatase-def.References"><h2 id="_m-sulfatase-def_References_">References</h2><div id="m-sulfatase-def.Literature_Cited"><h3>Literature Cited</h3><ul class="simple-list"><li class="half_rhythm"><p><div class="bk_ref" id="m-sulfatase-def.REF.adang.2017.18">Adang LA, Sherbini O, Ball L, Bloom M, Darbari A, Amartino H, DiVito D, Eichler F, Escolar M, Evans SH, Fatemi A, Fraser J, Hollowell L, Jaffe N, Joseph C, Karpinski M, Keller S, Maddock R, Mancilla E, McClary B, Mertz J, Morgart K, Langan T, Leventer R, Parikh S, Pizzino A, Prange E, Renaud DL, Rizzo W, Shapiro J, Suhr D, Suhr T, Tonduti D, Waggoner J, Waldman A, Wolf NI, Zerem A, Bonkowsky JL, Bernard G, van Haren K, Vanderver A, et al. 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ERp44 mediates a thiol-independent retention of formylglycine-generating enzyme in the endoplasmic reticulum. <span><span class="ref-journal">J Biol Chem. </span>2008b;<span class="ref-vol">283</span>:6375–83.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/18178549" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18178549</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="m-sulfatase-def.REF.meng.2013.836">Meng Y, Zhang WM, Shi HP, Yao FX, Qiu ZQ, Yang T, Zhao SM, Huang SZ. Clinical characterization and mutation identification for multiple sulfatase deficiency patients in China. <span><span class="ref-journal">Zhonghua Er Ke Za Zhi. </span>2013;<span class="ref-vol">51</span>:836–41.</span> [Chinese J Pediatr] [<a href="https://pubmed.ncbi.nlm.nih.gov/24484558" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24484558</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="m-sulfatase-def.REF.meshach_paul.2018.3575">Meshach Paul D, Chadah T, Senthilkumar B, Sethumadhavan R, Rajasekaran R. Structural distortions due to missense mutations in human formylglycine-generating enzyme leading to multiple sulfatase deficiency. <span><span class="ref-journal">J Biomol Struct Dyn. </span>2018;<span class="ref-vol">36</span>:3575–85.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/29048999" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 29048999</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="m-sulfatase-def.REF.miskin.2016.98">Miskin C, Melvin JJ, Legido A, Wenger DA, Harasink SM, Khurana DS. A patient with atypical multiple sulfatase deficiency. <span><span class="ref-journal">Pediatr Neurol. </span>2016;<span class="ref-vol">57</span>:98–100.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/26825355" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26825355</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="m-sulfatase-def.REF.prasad.2014.626">Prasad C, Rupar CA, Campbell C, Napier M, Ramsay D, Tay KY, Sharan S, Prasad AN. Case of multiple sulfatase deficiency and ocular albinism: a diagnostic odyssey. <span><span class="ref-journal">Can J Neurol Sci. </span>2014;<span class="ref-vol">41</span>:626–31.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/25373814" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25373814</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="m-sulfatase-def.REF.preusserkunze.2005.14900">Preusser-Kunze A, Mariappan M, Schmidt B, Gande SL, Mutenda K, Wenzel D, von Figura K, Dierks T. Molecular characterization of the human Cα-formylglycine-generating enzyme. <span><span class="ref-journal">J Biol Chem. </span>2005;<span class="ref-vol">280</span>:14900–10.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/15657036" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15657036</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="m-sulfatase-def.REF.sabourdy.2015.31">Sabourdy F, Mourey L, Le Trionnaire E, Bednarek N, Caillaud C, Chaix Y, Delrue MA, Dusser A, Froissart R, Garnotel R, Guffon N, Megarbane A, Ogier de Baulny H, Pédespan JM, Pichard S, Valayannopoulos V, Verloes A, Levade T. Natural disease history and characterisation of SUMF1 molecular defects in ten unrelated patients with multiple sulfatase deficiency. <span><span class="ref-journal">Orphanet J Rare Dis. </span>2015;<span class="ref-vol">10</span>:31.</span> [<a href="/pmc/articles/PMC4375846/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4375846</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/25885655" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25885655</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="m-sulfatase-def.REF.santos.2006.955">Santos RP, Hoo JJ. Difficulty in recognizing multiple sulfatase deficiency in an infant. <span><span class="ref-journal">Pediatrics. </span>2006;<span class="ref-vol">117</span>:955–8.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/16510683" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16510683</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="m-sulfatase-def.REF.sardiello.2005.3203">Sardiello M, Annunziata I, Roma G, Ballabio A. Sulfatases and sulfatase modifying factors: an exclusive and promiscuous relationship. <span><span class="ref-journal">Hum Mol Genet. </span>2005;<span class="ref-vol">14</span>:3203–17.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/16174644" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16174644</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="m-sulfatase-def.REF.schlotawa.2011.253">Schlotawa L, Ennemann EC, Radhakrishnan K, Schmidt B, Chakrapani A, Christen HJ, Moser H, Steinmann B, Dierks T, Gärtner J. SUMF1 mutations affecting stability and activity of formylglycine generating enzyme predict clinical outcome in multiple sulfatase deficiency. <span><span class="ref-journal">Eur J Hum Genet. </span>2011;<span class="ref-vol">19</span>:253–61.</span> [<a href="/pmc/articles/PMC3062010/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3062010</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/21224894" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21224894</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="m-sulfatase-def.REF.schlotawa.2013">Schlotawa L, Radhakrishnan K, Baumgartner M, Schmid R, Schmidt B, Dierks T, Gärtner J. Rapid degradation of an active formylglycine generating enzyme variant leads to a late infantile severe form of multiple sulfatase deficiency. 2013;21:1020–3. [<a href="/pmc/articles/PMC3746267/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3746267</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/23321616" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23321616</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="m-sulfatase-def.REF.schlotawa.2008.205">Schlotawa L, Steinfeld R, von Figura K, Dierks T, Gärtner J. Molecular analysis of SUMF1 mutations: stability and residual activity of mutant formylglycine-generating enzyme determine disease severity in multiple sulfatase deficiency. <span><span class="ref-journal">Hum Mutat. </span>2008;<span class="ref-vol">29</span>:205.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/18157819" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18157819</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="m-sulfatase-def.REF.schlotawa.2018.27">Schlotawa L, Wachs M, Bernhard O, Mayer FJ, Dierks T, Schmidt B, Radhakrishnan K. Recognition and ER quality control of misfolded formylglycine-generating enzyme by protein disulfide isomerase. <span><span class="ref-journal">Cell Rep. </span>2018;<span class="ref-vol">24</span>:27–37.e4.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/29972788" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 29972788</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="m-sulfatase-def.REF.settembre.2008.119">Settembre C, Fraldi A, Jahreiss L, Spampanato C, Venturi C, Medina D, de Pablo R, Tacchetti C, Rubinsztein DC, Ballabio A. A block of autophagy in lysosomal storage disorders. <span><span class="ref-journal">Hum Mol Genet. </span>2008;<span class="ref-vol">17</span>:119–29.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/17913701" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17913701</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="m-sulfatase-def.REF.van_der_knaap.2013">van der Knaap MS, Valk J. <em>Magnetic Resonance of Myelin, Myelination and Myelin Disorders.</em> Springer Science & Business Media. 2013.</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="m-sulfatase-def.REF.zilberman.2016.95">Zilberman U, Bibi H. The effect of multiple sulfatase deficiency (MSD) on dental development: can we use the teeth as an early diagnostic tool? <span><span class="ref-journal">JIMD Rep. </span>2016;<span class="ref-vol">30</span>:95–101.</span> [<a href="/pmc/articles/PMC5110438/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5110438</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/27344646" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27344646</span></a>]</div></p></li></ul></div></div><div id="bk_toc_contnr"></div></div></div><div class="fm-sec"><h2 id="_NBK538937_pubdet_">Publication Details</h2><h3>Author Information and Affiliations</h3><div class="contrib half_rhythm"><span itemprop="author">Lars Schlotawa</span>, MD<div class="affiliation small">University Medical Center Göttingen<br />Göttingen, Germany<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="ed.negnitteog-inu.dem@awatolhcs.sral" class="oemail">ed.negnitteog-inu.dem@awatolhcs.sral</a></div></div></div><div class="contrib half_rhythm"><span itemprop="author">Laura Adang</span>, MD, PhD<div class="affiliation small">The Children's Hospital of Philadelphia<br />Philadelphia, Pennsylvania<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="ude.pohc.liame@lgnada" class="oemail">ude.pohc.liame@lgnada</a></div></div></div><div class="contrib half_rhythm"><span itemprop="author">Mauricio De Castro</span>, MD<div class="affiliation small">Keesler Air Force Base<br />Biloxi, Mississippi<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="lim.liam@lim.tleterportsaced.j.oiciruam" class="oemail">lim.liam@lim.tleterportsaced.j.oiciruam</a></div></div></div><div class="contrib half_rhythm"><span itemprop="author">Rebecca Ahrens-Nicklas</span>, MD, PhD<div class="affiliation small">The Children's Hospital of Philadelphia<br />Philadelphia, Pennsylvania<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="ude.pohc.liame@rsalkcinsnerha" class="oemail">ude.pohc.liame@rsalkcinsnerha</a></div></div></div><h3>Publication History</h3><p class="small">Initial Posting: <span itemprop="datePublished">March 21, 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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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>Schlotawa L, Adang L, De Castro M, et al. Multiple Sulfatase Deficiency. 2019 Mar 21. 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/edm-ad/?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/myhre/?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="figobmsulfatasedefTmoleculargenetictest"><div id="m-sulfatase-def.T.molecular_genetic_test" class="table"><h3><span class="label">Table 1. </span></h3><div class="caption"><p>Molecular Genetic Testing Used in Multiple Sulfatase Deficiency</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK538937/table/m-sulfatase-def.T.molecular_genetic_test/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__m-sulfatase-def.T.molecular_genetic_test_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_m-sulfatase-def.T.molecular_genetic_test_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_m-sulfatase-def.T.molecular_genetic_test_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Method</th><th id="hd_h_m-sulfatase-def.T.molecular_genetic_test_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Proportion of Pathogenic Variants <sup>2</sup> Detectable by This Method</th></tr></thead><tbody><tr><td headers="hd_h_m-sulfatase-def.T.molecular_genetic_test_1_1_1_1" rowspan="2" scope="row" 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_m-sulfatase-def.T.molecular_genetic_test_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Sequence analysis <sup>3</sup></td><td headers="hd_h_m-sulfatase-def.T.molecular_genetic_test_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">~98%-99% <sup>5</sup></td></tr><tr><td headers="hd_h_m-sulfatase-def.T.molecular_genetic_test_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Gene-targeted deletion/duplication analysis <sup>4</sup></td><td headers="hd_h_m-sulfatase-def.T.molecular_genetic_test_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">~1.5% <sup>5</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="m-sulfatase-def.TF.1.1"><p class="no_margin">See <a href="/books/NBK538937/?report=reader#m-sulfatase-def.molgen.TA">Table A. Genes and Databases</a> for chromosome locus and protein.</p></div></dd></dl><dl class="bkr_refwrap"><dt>2. </dt><dd><div id="m-sulfatase-def.TF.1.2"><p class="no_margin">See <a href="#m-sulfatase-def.Molecular_Genetics">Molecular Genetics</a> for information on allelic variants detected in this gene.</p></div></dd></dl><dl class="bkr_refwrap"><dt>3. </dt><dd><div id="m-sulfatase-def.TF.1.3"><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>4. </dt><dd><div id="m-sulfatase-def.TF.1.4"><p class="no_margin">Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include a range of techniques such as quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications.</p></div></dd></dl><dl class="bkr_refwrap"><dt>5. </dt><dd><div id="m-sulfatase-def.TF.1.5"><p class="no_margin">Review of all available cases in the literature revealed three large deletions and no duplications out of 201 alleles [Author observation, in preparation for publication].</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobmsulfatasedefTdisorderstoconsider"><div id="m-sulfatase-def.T.disorders_to_consider" class="table"><h3><span class="label">Table 2. </span></h3><div class="caption"><p>Disorders to Consider in the Differential Diagnosis of Multiple Sulfatase Deficiency (MSD)</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK538937/table/m-sulfatase-def.T.disorders_to_consider/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__m-sulfatase-def.T.disorders_to_consider_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_m-sulfatase-def.T.disorders_to_consider_1_1_1_1" rowspan="2" scope="col" colspan="1" headers="hd_h_m-sulfatase-def.T.disorders_to_consider_1_1_1_1" style="text-align:left;vertical-align:middle;">Disorder</th><th id="hd_h_m-sulfatase-def.T.disorders_to_consider_1_1_1_2" rowspan="2" scope="col" colspan="1" headers="hd_h_m-sulfatase-def.T.disorders_to_consider_1_1_1_2" style="text-align:left;vertical-align:middle;">Gene(s)</th><th id="hd_h_m-sulfatase-def.T.disorders_to_consider_1_1_1_3" rowspan="2" scope="col" colspan="1" headers="hd_h_m-sulfatase-def.T.disorders_to_consider_1_1_1_3" style="text-align:left;vertical-align:middle;">MOI</th><th id="hd_h_m-sulfatase-def.T.disorders_to_consider_1_1_1_4" colspan="2" scope="colgroup" rowspan="1" style="text-align:left;vertical-align:middle;">Clinical Features of Differential Diagnosis Disorder</th></tr><tr><th headers="hd_h_m-sulfatase-def.T.disorders_to_consider_1_1_1_4" id="hd_h_m-sulfatase-def.T.disorders_to_consider_1_1_2_1" colspan="1" scope="colgroup" rowspan="1" style="text-align:left;vertical-align:middle;">Overlapping w/MSD</th><th headers="hd_h_m-sulfatase-def.T.disorders_to_consider_1_1_1_4" id="hd_h_m-sulfatase-def.T.disorders_to_consider_1_1_2_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Distinguishing from MSD</th></tr></thead><tbody><tr><td headers="hd_h_m-sulfatase-def.T.disorders_to_consider_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><a href="/books/n/gene/mld/?report=reader">Arylsulfatase A deficiency</a> (metachromatic leukodystrophy; MLD)</td><td headers="hd_h_m-sulfatase-def.T.disorders_to_consider_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>ARSA</i>
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</td><td headers="hd_h_m-sulfatase-def.T.disorders_to_consider_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_m-sulfatase-def.T.disorders_to_consider_1_1_1_4 hd_h_m-sulfatase-def.T.disorders_to_consider_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">All MLD features can be found in MSD, incl central & peripheral demyelination & progressive neurologic deterioration</td><td headers="hd_h_m-sulfatase-def.T.disorders_to_consider_1_1_1_4 hd_h_m-sulfatase-def.T.disorders_to_consider_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Absence of other systemic findings assoc w/MSD</td></tr><tr><td headers="hd_h_m-sulfatase-def.T.disorders_to_consider_1_1_1_1" scope="row" rowspan="1" colspan="1" style="background-color:rgb(242,242,242);text-align:left;vertical-align:middle;">Saposin B deficiency (OMIM <a href="https://omim.org/entry/249900" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">249900</a>)</td><td headers="hd_h_m-sulfatase-def.T.disorders_to_consider_1_1_1_2" rowspan="1" colspan="1" style="background-color:rgb(242,242,242);text-align:left;vertical-align:middle;">
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<i>PSAP</i>
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</td><td headers="hd_h_m-sulfatase-def.T.disorders_to_consider_1_1_1_3" rowspan="1" colspan="1" style="background-color:rgb(242,242,242);text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_m-sulfatase-def.T.disorders_to_consider_1_1_1_4 hd_h_m-sulfatase-def.T.disorders_to_consider_1_1_2_1" rowspan="1" colspan="1" style="background-color:rgb(242,242,242);text-align:left;vertical-align:middle;">All saposin B deficiency features can be found in MSD, incl central & peripheral demyelination & progressive neurologic deterioration</td><td headers="hd_h_m-sulfatase-def.T.disorders_to_consider_1_1_1_4 hd_h_m-sulfatase-def.T.disorders_to_consider_1_1_2_2" rowspan="1" colspan="1" style="background-color:rgb(242,242,242);text-align:left;vertical-align:middle;">Absence of other systemic findings assoc w/MSD</td></tr><tr><td headers="hd_h_m-sulfatase-def.T.disorders_to_consider_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><a href="/books/n/gene/ml2/?report=reader">Mucolipidosis II</a> (I-cell disease)</td><td headers="hd_h_m-sulfatase-def.T.disorders_to_consider_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>GNPTAB</i>
|
|
</td><td headers="hd_h_m-sulfatase-def.T.disorders_to_consider_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_m-sulfatase-def.T.disorders_to_consider_1_1_1_4 hd_h_m-sulfatase-def.T.disorders_to_consider_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Severe infantile onset, progressive neurologic deterioration, skeletal deformities (incl dysostosis multiplex), postnatal growth restriction, cardiac involvement, skin thickening, recurrent ear infections</td><td headers="hd_h_m-sulfatase-def.T.disorders_to_consider_1_1_1_4 hd_h_m-sulfatase-def.T.disorders_to_consider_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Severe contractures (although joint mobility issues may be seen in MSD)</td></tr><tr><td headers="hd_h_m-sulfatase-def.T.disorders_to_consider_1_1_1_1" scope="row" rowspan="1" colspan="1" style="background-color:rgb(242,242,242);text-align:left;vertical-align:middle;">
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<a href="/books/n/gene/krabbe/?report=reader">Krabbe disease</a>
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</td><td headers="hd_h_m-sulfatase-def.T.disorders_to_consider_1_1_1_2" rowspan="1" colspan="1" style="background-color:rgb(242,242,242);text-align:left;vertical-align:middle;">
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<i>GALC</i>
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</td><td headers="hd_h_m-sulfatase-def.T.disorders_to_consider_1_1_1_3" rowspan="1" colspan="1" style="background-color:rgb(242,242,242);text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_m-sulfatase-def.T.disorders_to_consider_1_1_1_4 hd_h_m-sulfatase-def.T.disorders_to_consider_1_1_2_1" rowspan="1" colspan="1" style="background-color:rgb(242,242,242);text-align:left;vertical-align:middle;">Central & peripheral demyelination, progressive neurologic deterioration</td><td headers="hd_h_m-sulfatase-def.T.disorders_to_consider_1_1_1_4 hd_h_m-sulfatase-def.T.disorders_to_consider_1_1_2_2" rowspan="1" colspan="1" style="background-color:rgb(242,242,242);text-align:left;vertical-align:middle;">Absence of: cardiac & ophthalmologic complications, skeletal involvement (incl dysostosis multiplex), ichthyosis, hydrocephalus, hepatosplenomegaly, oral & dental issues, hearing loss, recurrent ear infections, upper airway obstruction</td></tr><tr><td headers="hd_h_m-sulfatase-def.T.disorders_to_consider_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="/books/n/gene/alexander/?report=reader">Alexander disease</a>
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</td><td headers="hd_h_m-sulfatase-def.T.disorders_to_consider_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>GFAP</i>
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</td><td headers="hd_h_m-sulfatase-def.T.disorders_to_consider_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD</td><td headers="hd_h_m-sulfatase-def.T.disorders_to_consider_1_1_1_4 hd_h_m-sulfatase-def.T.disorders_to_consider_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Central demyelination & hydrocephalus, progressive neurologic deterioration</td><td headers="hd_h_m-sulfatase-def.T.disorders_to_consider_1_1_1_4 hd_h_m-sulfatase-def.T.disorders_to_consider_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Absence of: cardiac & ophthalmologic complications, skeletal involvement (incl dysostosis multiplex), ichthyosis, hepatosplenomegaly, oral & dental issues, hearing loss, recurrent ear infections, upper airway obstruction</td></tr><tr><td headers="hd_h_m-sulfatase-def.T.disorders_to_consider_1_1_1_1" scope="row" rowspan="1" colspan="1" style="background-color:rgb(242,242,242);text-align:left;vertical-align:middle;">
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<a href="/books/n/gene/canavan/?report=reader">Canavan disease</a>
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</td><td headers="hd_h_m-sulfatase-def.T.disorders_to_consider_1_1_1_2" rowspan="1" colspan="1" style="background-color:rgb(242,242,242);text-align:left;vertical-align:middle;">
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<i>ASPA</i>
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|
</td><td headers="hd_h_m-sulfatase-def.T.disorders_to_consider_1_1_1_3" rowspan="1" colspan="1" style="background-color:rgb(242,242,242);text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_m-sulfatase-def.T.disorders_to_consider_1_1_1_4 hd_h_m-sulfatase-def.T.disorders_to_consider_1_1_2_1" rowspan="1" colspan="1" style="background-color:rgb(242,242,242);text-align:left;vertical-align:middle;">Central demyelination, progressive neurologic deterioration, macrocephaly</td><td headers="hd_h_m-sulfatase-def.T.disorders_to_consider_1_1_1_4 hd_h_m-sulfatase-def.T.disorders_to_consider_1_1_2_2" rowspan="1" colspan="1" style="background-color:rgb(242,242,242);text-align:left;vertical-align:middle;">Absence of: cardiac & ophthalmologic complications, skeletal involvement (incl dysotosis multiplex), ichthyosis, hepatosplenomegaly, oral & dental issues, hearing loss, recurrent ear infections, upper airway obstruction</td></tr><tr><td headers="hd_h_m-sulfatase-def.T.disorders_to_consider_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Fucosidosis (OMIM <a href="https://omim.org/entry/230000" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">230000</a>)</td><td headers="hd_h_m-sulfatase-def.T.disorders_to_consider_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>FUCA1</i>
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|
</td><td headers="hd_h_m-sulfatase-def.T.disorders_to_consider_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_m-sulfatase-def.T.disorders_to_consider_1_1_1_4 hd_h_m-sulfatase-def.T.disorders_to_consider_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Progressive neurologic deterioration, dysostosis multiplex, coarse facial features</td><td headers="hd_h_m-sulfatase-def.T.disorders_to_consider_1_1_1_4 hd_h_m-sulfatase-def.T.disorders_to_consider_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Absence of: cardiac & ophthalmologic complications, ichthyosis, hepatosplenomegaly, oral & dental issues, hearing loss, recurrent ear infections, upper airway obstruction</td></tr><tr><td headers="hd_h_m-sulfatase-def.T.disorders_to_consider_1_1_1_1" scope="row" rowspan="1" colspan="1" style="background-color:rgb(242,242,242);text-align:left;vertical-align:middle;"><a href="/books/n/gene/mps1/?report=reader">MPS I</a> <sup>1</sup></td><td headers="hd_h_m-sulfatase-def.T.disorders_to_consider_1_1_1_2" rowspan="1" colspan="1" style="background-color:rgb(242,242,242);text-align:left;vertical-align:middle;">
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<i>IDUA</i>
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|
</td><td headers="hd_h_m-sulfatase-def.T.disorders_to_consider_1_1_1_3" rowspan="1" colspan="1" style="background-color:rgb(242,242,242);text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_m-sulfatase-def.T.disorders_to_consider_1_1_1_4 hd_h_m-sulfatase-def.T.disorders_to_consider_1_1_2_1" rowspan="1" colspan="1" style="background-color:rgb(242,242,242);text-align:left;vertical-align:middle;">DD, skeletal involvement, growth restriction, corneal clouding, cardiac involvement, hepatosplenomegaly, dysmorphic features</td><td headers="hd_h_m-sulfatase-def.T.disorders_to_consider_1_1_1_4 hd_h_m-sulfatase-def.T.disorders_to_consider_1_1_2_2" rowspan="1" colspan="1" style="background-color:rgb(242,242,242);text-align:left;vertical-align:middle;">Facial dysmorphic features & cardiac involvement are more prominent in MPS I.</td></tr><tr><td headers="hd_h_m-sulfatase-def.T.disorders_to_consider_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><a href="/books/n/gene/hunter/?report=reader">MPS II</a> (Hunter syndrome)</td><td headers="hd_h_m-sulfatase-def.T.disorders_to_consider_1_1_1_2" 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_m-sulfatase-def.T.disorders_to_consider_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">XL</td><td headers="hd_h_m-sulfatase-def.T.disorders_to_consider_1_1_1_4 hd_h_m-sulfatase-def.T.disorders_to_consider_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">DD, short stature, skeletal involvement, hepatosplenomegaly, dysmorphic features</td><td headers="hd_h_m-sulfatase-def.T.disorders_to_consider_1_1_1_4 hd_h_m-sulfatase-def.T.disorders_to_consider_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Females rarely affected; corneal clouding not a typical feature</td></tr><tr><td headers="hd_h_m-sulfatase-def.T.disorders_to_consider_1_1_1_1" scope="row" rowspan="1" colspan="1" style="background-color:rgb(242,242,242);text-align:left;vertical-align:middle;">MPS III (Sanfilippo syndrome) (OMIM <a href="https://omim.org/entry/252900" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">252900</a>, <a href="https://omim.org/entry/252920" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">252920</a>, <a href="https://omim.org/entry/252930" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">252930</a>, <a href="https://omim.org/entry/252940" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">252940</a>)</td><td headers="hd_h_m-sulfatase-def.T.disorders_to_consider_1_1_1_2" rowspan="1" colspan="1" style="background-color:rgb(242,242,242);text-align:left;vertical-align:middle;">
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<i>GNS</i>
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|
<br />
|
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<i>HGSNAT</i>
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|
<br />
|
|
<i>NAGLU</i>
|
|
<br />
|
|
<i>SGSH</i>
|
|
</td><td headers="hd_h_m-sulfatase-def.T.disorders_to_consider_1_1_1_3" rowspan="1" colspan="1" style="background-color:rgb(242,242,242);text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_m-sulfatase-def.T.disorders_to_consider_1_1_1_4 hd_h_m-sulfatase-def.T.disorders_to_consider_1_1_2_1" rowspan="1" colspan="1" style="background-color:rgb(242,242,242);text-align:left;vertical-align:middle;">Neurodegeneration, DD, hepatosplenomegaly (<50% of persons w/Sanfilippo syndrome)</td><td headers="hd_h_m-sulfatase-def.T.disorders_to_consider_1_1_1_4 hd_h_m-sulfatase-def.T.disorders_to_consider_1_1_2_2" rowspan="1" colspan="1" style="background-color:rgb(242,242,242);text-align:left;vertical-align:middle;">May have slower, more insidious course presenting mainly w/cognitive & neurologic signs & symptoms</td></tr><tr><td headers="hd_h_m-sulfatase-def.T.disorders_to_consider_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">MPS IV (Morquio syndrome) (See <a href="/books/n/gene/mps4a/?report=reader">MPS IVA</a>, <a href="/books/n/gene/gm1-ganglio/?report=reader"><i>GLB1</i>-Related Disorders</a>.)</td><td headers="hd_h_m-sulfatase-def.T.disorders_to_consider_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>GALNS</i>
|
|
<br />
|
|
<i>GLB1</i>
|
|
</td><td headers="hd_h_m-sulfatase-def.T.disorders_to_consider_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_m-sulfatase-def.T.disorders_to_consider_1_1_1_4 hd_h_m-sulfatase-def.T.disorders_to_consider_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Skeletal involvement, hearing loss, facial dysmorphic features</td><td headers="hd_h_m-sulfatase-def.T.disorders_to_consider_1_1_1_4 hd_h_m-sulfatase-def.T.disorders_to_consider_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">More severe skeletal involvement; MPS IVA does not present w/ID.</td></tr><tr><td headers="hd_h_m-sulfatase-def.T.disorders_to_consider_1_1_1_1" scope="row" rowspan="1" colspan="1" style="background-color:rgb(242,242,242);text-align:left;vertical-align:middle;">MPS VI (Maroteaux-Lamy syndrome) (OMIM <a href="https://omim.org/entry/253200" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">253200</a>)</td><td headers="hd_h_m-sulfatase-def.T.disorders_to_consider_1_1_1_2" rowspan="1" colspan="1" style="background-color:rgb(242,242,242);text-align:left;vertical-align:middle;">
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<i>ARSB</i>
|
|
</td><td headers="hd_h_m-sulfatase-def.T.disorders_to_consider_1_1_1_3" rowspan="1" colspan="1" style="background-color:rgb(242,242,242);text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_m-sulfatase-def.T.disorders_to_consider_1_1_1_4 hd_h_m-sulfatase-def.T.disorders_to_consider_1_1_2_1" rowspan="1" colspan="1" style="background-color:rgb(242,242,242);text-align:left;vertical-align:middle;">Dysmorphic features, hepatosplenomegaly, short stature, corneal clouding, skeletal involvement</td><td headers="hd_h_m-sulfatase-def.T.disorders_to_consider_1_1_1_4 hd_h_m-sulfatase-def.T.disorders_to_consider_1_1_2_2" rowspan="1" colspan="1" style="background-color:rgb(242,242,242);text-align:left;vertical-align:middle;">More severe skeletal involvement; absence of ID</td></tr><tr><td headers="hd_h_m-sulfatase-def.T.disorders_to_consider_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">X-linked ichthyosis (OMIM <a href="https://omim.org/entry/308100" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">308100</a>)</td><td headers="hd_h_m-sulfatase-def.T.disorders_to_consider_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>STS</i>
|
|
</td><td headers="hd_h_m-sulfatase-def.T.disorders_to_consider_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">XL</td><td headers="hd_h_m-sulfatase-def.T.disorders_to_consider_1_1_1_4 hd_h_m-sulfatase-def.T.disorders_to_consider_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Corneal opacities, ichthyosis</td><td headers="hd_h_m-sulfatase-def.T.disorders_to_consider_1_1_1_4 hd_h_m-sulfatase-def.T.disorders_to_consider_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Females rarely affected; absence of DD & neurodegeneration</td></tr><tr><td headers="hd_h_m-sulfatase-def.T.disorders_to_consider_1_1_1_1" scope="row" rowspan="1" colspan="1" style="background-color:rgb(242,242,242);text-align:left;vertical-align:middle;">
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|
<a href="/books/n/gene/cdp1-xlr/?report=reader">Chondrodysplasia punctata 1, X-linked</a>
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|
</td><td headers="hd_h_m-sulfatase-def.T.disorders_to_consider_1_1_1_2" rowspan="1" colspan="1" style="background-color:rgb(242,242,242);text-align:left;vertical-align:middle;"><i>ARSL</i> (<i>ARSE</i>)</td><td headers="hd_h_m-sulfatase-def.T.disorders_to_consider_1_1_1_3" rowspan="1" colspan="1" style="background-color:rgb(242,242,242);text-align:left;vertical-align:middle;">XLR</td><td headers="hd_h_m-sulfatase-def.T.disorders_to_consider_1_1_1_4 hd_h_m-sulfatase-def.T.disorders_to_consider_1_1_2_1" rowspan="1" colspan="1" style="background-color:rgb(242,242,242);text-align:left;vertical-align:middle;">DD in 15%-20% of affected persons, short stature, epiphyseal stippling, cataracts, hearing loss</td><td headers="hd_h_m-sulfatase-def.T.disorders_to_consider_1_1_1_4 hd_h_m-sulfatase-def.T.disorders_to_consider_1_1_2_2" rowspan="1" colspan="1" style="background-color:rgb(242,242,242);text-align:left;vertical-align:middle;">Females rarely affected; characteristic facial appearance; absence of neurodegeneration</td></tr><tr><td headers="hd_h_m-sulfatase-def.T.disorders_to_consider_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><a href="/books/n/gene/tay-sachs/?report=reader">Hexosaminidase A deficiency</a> (Tay-Sachs disease)</td><td headers="hd_h_m-sulfatase-def.T.disorders_to_consider_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>HEXA</i>
|
|
</td><td headers="hd_h_m-sulfatase-def.T.disorders_to_consider_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_m-sulfatase-def.T.disorders_to_consider_1_1_1_4 hd_h_m-sulfatase-def.T.disorders_to_consider_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Progressive neurodegeneration, DD, spasticity, blindness, death in infancy</td><td headers="hd_h_m-sulfatase-def.T.disorders_to_consider_1_1_1_4 hd_h_m-sulfatase-def.T.disorders_to_consider_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Cherry red spot of the fovea <sup>2</sup>; absence of skeletal abnormalities & hepatomegaly</td></tr><tr><td headers="hd_h_m-sulfatase-def.T.disorders_to_consider_1_1_1_1" scope="row" rowspan="1" colspan="1" style="background-color:rgb(242,242,242);text-align:left;vertical-align:middle;">Hexosaminidase A/B deficiency (<a href="/books/n/gene/sandhoff/?report=reader">Sandhoff disease</a>)</td><td headers="hd_h_m-sulfatase-def.T.disorders_to_consider_1_1_1_2" rowspan="1" colspan="1" style="background-color:rgb(242,242,242);text-align:left;vertical-align:middle;">
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<i>HEXB</i>
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</td><td headers="hd_h_m-sulfatase-def.T.disorders_to_consider_1_1_1_3" rowspan="1" colspan="1" style="background-color:rgb(242,242,242);text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_m-sulfatase-def.T.disorders_to_consider_1_1_1_4 hd_h_m-sulfatase-def.T.disorders_to_consider_1_1_2_1" rowspan="1" colspan="1" style="background-color:rgb(242,242,242);text-align:left;vertical-align:middle;">Progressive neurodegeneration, DD, spasticity, blindness, death in infancy</td><td headers="hd_h_m-sulfatase-def.T.disorders_to_consider_1_1_1_4 hd_h_m-sulfatase-def.T.disorders_to_consider_1_1_2_2" rowspan="1" colspan="1" style="background-color:rgb(242,242,242);text-align:left;vertical-align:middle;">Cherry red spot & ↑ startle response <sup>3</sup>; hepatomegaly & skeletal abnormalities are less common than in MSD</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">AD = autosomal dominant, AR = autosomal recessive, MOI = mode of inheritance: XL = X-linked; DD = developmental delay; ID = intellectual disability; MPS = mucopolysaccharidosis</p></div></dd></dl><dl class="bkr_refwrap"><dt>1. </dt><dd><div id="m-sulfatase-def.TF.2.1"><p class="no_margin">Severe or attenuated MPS I; Note: while individuals with MPS I have traditionally been classified as having one of three MPS I syndromes (Hurler syndrome, Hurler-Scheie syndrome, or Scheie syndrome), no easily measurable biochemical differences have been identified and the clinical findings overlap; thus, affected individuals are best described as having either severe or attenuated MPS I.</p></div></dd></dl><dl class="bkr_refwrap"><dt>2. </dt><dd><div id="m-sulfatase-def.TF.2.2"><p class="no_margin">Cherry red spot of the fovea is not a typical finding in MSD.</p></div></dd></dl><dl class="bkr_refwrap"><dt>3. </dt><dd><div id="m-sulfatase-def.TF.2.3"><p class="no_margin">Cherry red spot and increased startle response are not typical findings in MSD.</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobmsulfatasedefTrecommendedevaluation"><div id="m-sulfatase-def.T.recommended_evaluation" class="table"><h3><span class="label">Table 3. </span></h3><div class="caption"><p>Recommended Evaluations Following Initial Diagnosis in Individuals with Multiple Sulfatase Deficiency</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK538937/table/m-sulfatase-def.T.recommended_evaluation/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__m-sulfatase-def.T.recommended_evaluation_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_m-sulfatase-def.T.recommended_evaluation_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">System/Concern</th><th id="hd_h_m-sulfatase-def.T.recommended_evaluation_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Evaluation</th><th id="hd_h_m-sulfatase-def.T.recommended_evaluation_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Comment</th></tr></thead><tbody><tr><td headers="hd_h_m-sulfatase-def.T.recommended_evaluation_1_1_1_1" rowspan="3" 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_m-sulfatase-def.T.recommended_evaluation_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Consultation w/neurologist</td><td headers="hd_h_m-sulfatase-def.T.recommended_evaluation_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Due to risk for central & peripheral demyelination, seizures, & hydrocephalus</td></tr><tr><td headers="hd_h_m-sulfatase-def.T.recommended_evaluation_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Consideration of brain imaging</td><td headers="hd_h_m-sulfatase-def.T.recommended_evaluation_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>To assess for hydrocephalus w/↑ intracranial pressure</div></li><li class="half_rhythm"><div>Consider urgent head imaging for any rapid neurologic changes.</div></li></ul>
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</td></tr><tr><td headers="hd_h_m-sulfatase-def.T.recommended_evaluation_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">EEG</td><td headers="hd_h_m-sulfatase-def.T.recommended_evaluation_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">If seizures are suspected</td></tr><tr><td headers="hd_h_m-sulfatase-def.T.recommended_evaluation_1_1_1_1" rowspan="2" 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_m-sulfatase-def.T.recommended_evaluation_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Consideration of spine imaging (radiographs &/or MRI), incl C-spine images</td><td headers="hd_h_m-sulfatase-def.T.recommended_evaluation_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>To assess for spine instability or stenosis leading to cord compression</div></li><li class="half_rhythm"><div>Consultation w/neurosurgeon as indicated</div></li></ul>
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</td></tr><tr><td headers="hd_h_m-sulfatase-def.T.recommended_evaluation_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Assessment of overall bone health w/consideration of 25(OH) vitamin D levels</td><td headers="hd_h_m-sulfatase-def.T.recommended_evaluation_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">If clinical concerns, addl testing (e.g., DXA scan) can be obtained.</td></tr><tr><td headers="hd_h_m-sulfatase-def.T.recommended_evaluation_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Ophthalmologic</b>
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</td><td headers="hd_h_m-sulfatase-def.T.recommended_evaluation_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Consultation w/ophthalmologist for eval of eye complications & measurement of intraophthalmic pressure</td><td headers="hd_h_m-sulfatase-def.T.recommended_evaluation_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To assess for glaucoma, corneal clouding, retinopathy, strabismus, optic nerve abnormalities, & cataracts</td></tr><tr><td headers="hd_h_m-sulfatase-def.T.recommended_evaluation_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_m-sulfatase-def.T.recommended_evaluation_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Consultation w/cardiologist for baseline EKG & echocardiogram</td><td headers="hd_h_m-sulfatase-def.T.recommended_evaluation_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To assess for presence of cardiac hypertrophy, cardiac valve issues, arrhythmias, & hypertension</td></tr><tr><td headers="hd_h_m-sulfatase-def.T.recommended_evaluation_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Otolaryngologic</b>
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</td><td headers="hd_h_m-sulfatase-def.T.recommended_evaluation_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Audiologic evaluation, w/consideration of brain stem auditory-evoked response testing</td><td headers="hd_h_m-sulfatase-def.T.recommended_evaluation_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To assess for hearing loss</td></tr><tr><td headers="hd_h_m-sulfatase-def.T.recommended_evaluation_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Consultation w/otolaryngologists if neck manipulation &/or anesthesia is needed</td><td headers="hd_h_m-sulfatase-def.T.recommended_evaluation_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Consideration of direct airway visualization & C-spine imaging due to progressive airway obstruction (particularly w/neck hyperextension)</td></tr><tr><td headers="hd_h_m-sulfatase-def.T.recommended_evaluation_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Skin</b>
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</td><td headers="hd_h_m-sulfatase-def.T.recommended_evaluation_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Consider consultation w/dermatologist.</td><td headers="hd_h_m-sulfatase-def.T.recommended_evaluation_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">For those w/severe skin involvement or concerns for secondary infections</td></tr><tr><td headers="hd_h_m-sulfatase-def.T.recommended_evaluation_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Dental</b>
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</td><td headers="hd_h_m-sulfatase-def.T.recommended_evaluation_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Consider consultation w/pediatric dentist.</td><td headers="hd_h_m-sulfatase-def.T.recommended_evaluation_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To assess for tooth enamel abnormalities &/or hyperplastic gums</td></tr><tr><td headers="hd_h_m-sulfatase-def.T.recommended_evaluation_1_1_1_1" rowspan="3" scope="row" 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_m-sulfatase-def.T.recommended_evaluation_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Assessment of growth parameters & feeding ability</td><td headers="hd_h_m-sulfatase-def.T.recommended_evaluation_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Many persons w/MSD are unable to safely & efficiently meet caloric needs by mouth; consider alternate routes (e.g., gastrostomy tubes).</td></tr><tr><td headers="hd_h_m-sulfatase-def.T.recommended_evaluation_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Consideration of baseline swallowing study</td><td headers="hd_h_m-sulfatase-def.T.recommended_evaluation_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To assess for swallowing dysfunction</td></tr><tr><td headers="hd_h_m-sulfatase-def.T.recommended_evaluation_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Abdominal ultrasound & serum liver enzyme testing <sup>1</sup></td><td headers="hd_h_m-sulfatase-def.T.recommended_evaluation_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To assess for hepatosplenomegaly & liver dysfunction</td></tr><tr><td headers="hd_h_m-sulfatase-def.T.recommended_evaluation_1_1_1_1" rowspan="2" scope="row" 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_m-sulfatase-def.T.recommended_evaluation_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Consideration of baseline sleep study</td><td headers="hd_h_m-sulfatase-def.T.recommended_evaluation_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To assess for obstructive sleep apnea</td></tr><tr><td headers="hd_h_m-sulfatase-def.T.recommended_evaluation_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Consideration of pulmonary function assessment, end tidal CO<sub>2</sub>, &/or bronchoscopy</td><td headers="hd_h_m-sulfatase-def.T.recommended_evaluation_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To assess for obstructive &/or restrictive airway disease, central &peripheral apneas, recurrent pneumonia, & tracheomalacia</td></tr><tr><td headers="hd_h_m-sulfatase-def.T.recommended_evaluation_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Renal/metabolic</b>
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</td><td headers="hd_h_m-sulfatase-def.T.recommended_evaluation_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">As the renal dysfunction is under-characterized at this time, labs should be obtained as clinically indicated.</td><td headers="hd_h_m-sulfatase-def.T.recommended_evaluation_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Consider consultation w/nephrologist for those w/metabolic acidosis.</td></tr><tr><td headers="hd_h_m-sulfatase-def.T.recommended_evaluation_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Developmental</b>
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</td><td headers="hd_h_m-sulfatase-def.T.recommended_evaluation_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Developmental assessment</td><td headers="hd_h_m-sulfatase-def.T.recommended_evaluation_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To incl assessment of age-appropriate motor, speech/language, cognitive skills</td></tr><tr><td headers="hd_h_m-sulfatase-def.T.recommended_evaluation_1_1_1_1" rowspan="2" 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_m-sulfatase-def.T.recommended_evaluation_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Baseline measurement of sulfatase activity, urinary extretion of sulfatide, & GAGs</td><td headers="hd_h_m-sulfatase-def.T.recommended_evaluation_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Measurement of levels not needed for clinical monitoring</td></tr><tr><td headers="hd_h_m-sulfatase-def.T.recommended_evaluation_1_1_1_2" colspan="1" scope="col" rowspan="1" style="text-align:left;vertical-align:middle;">Consultation w/clinical geneticist &/or genetic counselor</td><td headers="hd_h_m-sulfatase-def.T.recommended_evaluation_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></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">DXA = dual-energy x-ray absorptiometry; GAGs = glycosaminoglycans</p></div></dd></dl><dl class="bkr_refwrap"><dt>1. </dt><dd><div id="m-sulfatase-def.TF.3.1"><p class="no_margin">Measurement of serum AST, ALT, and GGT</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobmsulfatasedefTtreatmentofmanifesta"><div id="m-sulfatase-def.T.treatment_of_manifesta" class="table"><h3><span class="label">Table 4. </span></h3><div class="caption"><p>Treatment of Manifestations in Individuals with Multiple Sulfatase Deficiency</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK538937/table/m-sulfatase-def.T.treatment_of_manifesta/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__m-sulfatase-def.T.treatment_of_manifesta_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_m-sulfatase-def.T.treatment_of_manifesta_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Manifestation/Concern</th><th id="hd_h_m-sulfatase-def.T.treatment_of_manifesta_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Treatment</th><th id="hd_h_m-sulfatase-def.T.treatment_of_manifesta_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_m-sulfatase-def.T.treatment_of_manifesta_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Progressive hydrocephalus</b>
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</td><td headers="hd_h_m-sulfatase-def.T.treatment_of_manifesta_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Standard management by neurosurgery</td><td headers="hd_h_m-sulfatase-def.T.treatment_of_manifesta_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Urgent head imaging should be considered in anyone w/sudden changes in neurologic status (e.g., altered mental status, ↑ vomiting)</td></tr><tr><td headers="hd_h_m-sulfatase-def.T.treatment_of_manifesta_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_m-sulfatase-def.T.treatment_of_manifesta_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Standard anti-seizure medication <sup>1</sup></td><td headers="hd_h_m-sulfatase-def.T.treatment_of_manifesta_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_m-sulfatase-def.T.treatment_of_manifesta_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Spasticity</b>
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</td><td headers="hd_h_m-sulfatase-def.T.treatment_of_manifesta_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Standard therapeutic options may incl baclofen &/or botulinum toxin type A.</td><td headers="hd_h_m-sulfatase-def.T.treatment_of_manifesta_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Physical therapy & physiatry consultations for optimization of mobility & tone</td></tr><tr><td headers="hd_h_m-sulfatase-def.T.treatment_of_manifesta_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Spine instability or stenosis</b>
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</td><td headers="hd_h_m-sulfatase-def.T.treatment_of_manifesta_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Referral to orthopedist &/or neurosurgeon</td><td headers="hd_h_m-sulfatase-def.T.treatment_of_manifesta_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_m-sulfatase-def.T.treatment_of_manifesta_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Poor bone health</b>
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</td><td headers="hd_h_m-sulfatase-def.T.treatment_of_manifesta_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Supplementation w/vitamin D</td><td headers="hd_h_m-sulfatase-def.T.treatment_of_manifesta_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Consider referral to endocrinology</td></tr><tr><td headers="hd_h_m-sulfatase-def.T.treatment_of_manifesta_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Encourage weight-bearing exercise as tolerated.</td><td headers="hd_h_m-sulfatase-def.T.treatment_of_manifesta_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Physical therapy & physiatry consultations for optimization of mobility & tone</td></tr><tr><td headers="hd_h_m-sulfatase-def.T.treatment_of_manifesta_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Glaucoma, strabismus, corneal clouding, &/or cataracts</b>
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</td><td headers="hd_h_m-sulfatase-def.T.treatment_of_manifesta_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Standard treatment per ophthalmologist</td><td headers="hd_h_m-sulfatase-def.T.treatment_of_manifesta_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_m-sulfatase-def.T.treatment_of_manifesta_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Cardiac hypertrophy, cardiac valve issues, arrhythmias, & hypertension</b>
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</td><td headers="hd_h_m-sulfatase-def.T.treatment_of_manifesta_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Standard therapy per cardiologist</td><td headers="hd_h_m-sulfatase-def.T.treatment_of_manifesta_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_m-sulfatase-def.T.treatment_of_manifesta_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Hearing loss</b>
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</td><td headers="hd_h_m-sulfatase-def.T.treatment_of_manifesta_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Treatment of SNHL & conductive hearing loss per ENT/audiologist <sup>2</sup></td><td headers="hd_h_m-sulfatase-def.T.treatment_of_manifesta_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_m-sulfatase-def.T.treatment_of_manifesta_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Anesthesia precautions</b>
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</td><td headers="hd_h_m-sulfatase-def.T.treatment_of_manifesta_1_1_1_2" rowspan="2" colspan="1" style="text-align:left;vertical-align:middle;">Safe airway maintenance particularly during procedures that may require neck hyperextension</td><td headers="hd_h_m-sulfatase-def.T.treatment_of_manifesta_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Due to progressive upper-airway obstruction & risk for cervical spine instability</td></tr><tr><td headers="hd_h_m-sulfatase-def.T.treatment_of_manifesta_1_1_1_3" colspan="1" scope="col" rowspan="1" style="text-align:left;vertical-align:middle;">Assessment of airway constriction so that if required, appropriate-size devices (e.g., endotracheal tubes) are used</td></tr><tr><td headers="hd_h_m-sulfatase-def.T.treatment_of_manifesta_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Poor growth</b>
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</td><td headers="hd_h_m-sulfatase-def.T.treatment_of_manifesta_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Standard treatment per nutrition specialists</td><td headers="hd_h_m-sulfatase-def.T.treatment_of_manifesta_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_m-sulfatase-def.T.treatment_of_manifesta_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
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<b>Feeding difficulties</b>
|
|
</td><td headers="hd_h_m-sulfatase-def.T.treatment_of_manifesta_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Consideration of alternative routes for nutrition (e.g., NG or G-tube)</td><td headers="hd_h_m-sulfatase-def.T.treatment_of_manifesta_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Speech therapy consultation if concerns re efficiency or safety of oral feeding; GI or surgery consultation as clinically indicated</td></tr><tr><td headers="hd_h_m-sulfatase-def.T.treatment_of_manifesta_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Tooth & gum anomalies</b>
|
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</td><td headers="hd_h_m-sulfatase-def.T.treatment_of_manifesta_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Standard treatment per pediatric dentist</td><td headers="hd_h_m-sulfatase-def.T.treatment_of_manifesta_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_m-sulfatase-def.T.treatment_of_manifesta_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
|
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<b>Obstructive sleep apnea</b>
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</td><td headers="hd_h_m-sulfatase-def.T.treatment_of_manifesta_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Many children w/MPS receive an adenoidectomy &/or tonsillectomy, although a higher complication rate should be noted.</td><td headers="hd_h_m-sulfatase-def.T.treatment_of_manifesta_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Consider referral to sleep medicine specialist &/or pulmonologist.</td></tr><tr><td headers="hd_h_m-sulfatase-def.T.treatment_of_manifesta_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Some children may benefit from ventilatory support (CPAP, BiPAP).</td><td headers="hd_h_m-sulfatase-def.T.treatment_of_manifesta_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Advanced testing such as PFTs & sleep studies can be considered.</td></tr><tr><td headers="hd_h_m-sulfatase-def.T.treatment_of_manifesta_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Respiratory issues</b>
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</td><td headers="hd_h_m-sulfatase-def.T.treatment_of_manifesta_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Standard treatment per pulmonologist</td><td headers="hd_h_m-sulfatase-def.T.treatment_of_manifesta_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></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">G = gastrostomy; NG = nasogastric; PFTs = pulmonary function tests</p></div></dd></dl><dl class="bkr_refwrap"><dt>1. </dt><dd><div id="m-sulfatase-def.TF.4.1"><p class="no_margin">Education of parents regarding common seizure presentations is appropriate. For information on non-medical interventions and coping strategies for parents or caregivers of children diagnosed with epilepsy, see <a href="https://www.epilepsy.com/tools-resources/forms-resources#Epilepsy-Foundation-Toolbox" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Epilepsy Foundation Toolbox</a>.</p></div></dd></dl><dl class="bkr_refwrap"><dt>2. </dt><dd><div id="m-sulfatase-def.TF.4.2"><p class="no_margin">See <a href="/books/n/gene/deafness-overview/?report=reader">Hereditary Hearing Loss and Deafness Overview</a> for details about treatment options.</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobmsulfatasedefTsurveillancetoconsid"><div id="m-sulfatase-def.T.surveillance_to_consid" class="table"><h3><span class="label">Table 5. </span></h3><div class="caption"><p>Surveillance to Consider for Individuals with Multiple Sulfatase Deficiency</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK538937/table/m-sulfatase-def.T.surveillance_to_consid/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__m-sulfatase-def.T.surveillance_to_consid_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_m-sulfatase-def.T.surveillance_to_consid_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">System/Concern</th><th id="hd_h_m-sulfatase-def.T.surveillance_to_consid_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Evaluation</th><th id="hd_h_m-sulfatase-def.T.surveillance_to_consid_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_m-sulfatase-def.T.surveillance_to_consid_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_m-sulfatase-def.T.surveillance_to_consid_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Head circumference measurement</td><td headers="hd_h_m-sulfatase-def.T.surveillance_to_consid_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">At each visit</td></tr><tr><td headers="hd_h_m-sulfatase-def.T.surveillance_to_consid_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Serial brain/spine imaging <sup>1</sup></td><td headers="hd_h_m-sulfatase-def.T.surveillance_to_consid_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">As needed based on symptoms</td></tr><tr><td headers="hd_h_m-sulfatase-def.T.surveillance_to_consid_1_1_1_1" rowspan="2" 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_m-sulfatase-def.T.surveillance_to_consid_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Vitamin D level <sup>2</sup></td><td headers="hd_h_m-sulfatase-def.T.surveillance_to_consid_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Annually or as needed</td></tr><tr><td headers="hd_h_m-sulfatase-def.T.surveillance_to_consid_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">C-spine imaging (radiographs &/or MRI)</td><td headers="hd_h_m-sulfatase-def.T.surveillance_to_consid_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Prior to any procedure (incl intubation) that requires neck extension</td></tr><tr><td headers="hd_h_m-sulfatase-def.T.surveillance_to_consid_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Ophthalmologic</b>
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</td><td headers="hd_h_m-sulfatase-def.T.surveillance_to_consid_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Eye exam & intraocular pressure assessment</td><td headers="hd_h_m-sulfatase-def.T.surveillance_to_consid_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">At least annually or as needed</td></tr><tr><td headers="hd_h_m-sulfatase-def.T.surveillance_to_consid_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_m-sulfatase-def.T.surveillance_to_consid_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Serial EKG & echocardiography <sup>3</sup></td><td headers="hd_h_m-sulfatase-def.T.surveillance_to_consid_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">At least annually</td></tr><tr><td headers="hd_h_m-sulfatase-def.T.surveillance_to_consid_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Otolaryngologic</b>
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</td><td headers="hd_h_m-sulfatase-def.T.surveillance_to_consid_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Audiology eval</td><td headers="hd_h_m-sulfatase-def.T.surveillance_to_consid_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">At least annually, or as needed</td></tr><tr><td headers="hd_h_m-sulfatase-def.T.surveillance_to_consid_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Gastrointestinal/</b>
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<br />
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<b>Nutrition</b>
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</td><td headers="hd_h_m-sulfatase-def.T.surveillance_to_consid_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Weight & height measurements</td><td headers="hd_h_m-sulfatase-def.T.surveillance_to_consid_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">W/all clinical assessments</td></tr><tr><td headers="hd_h_m-sulfatase-def.T.surveillance_to_consid_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Serial abdominal ultrasound eval <sup>4</sup></td><td headers="hd_h_m-sulfatase-def.T.surveillance_to_consid_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_m-sulfatase-def.T.surveillance_to_consid_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_m-sulfatase-def.T.surveillance_to_consid_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Consideration of sleep study& PFTs</td><td headers="hd_h_m-sulfatase-def.T.surveillance_to_consid_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Periodically</td></tr><tr><td headers="hd_h_m-sulfatase-def.T.surveillance_to_consid_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Renal/Metabolic</b>
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</td><td headers="hd_h_m-sulfatase-def.T.surveillance_to_consid_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Monitoring of blood & urine acid-base balance</td><td headers="hd_h_m-sulfatase-def.T.surveillance_to_consid_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">As clinically indicated & w/episodes of physiologic stress</td></tr><tr><td headers="hd_h_m-sulfatase-def.T.surveillance_to_consid_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Developmental</b>
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</td><td headers="hd_h_m-sulfatase-def.T.surveillance_to_consid_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Assessment of developmental milestones & current developmental level</td><td headers="hd_h_m-sulfatase-def.T.surveillance_to_consid_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">At each visit</td></tr><tr><td headers="hd_h_m-sulfatase-def.T.surveillance_to_consid_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Neuropsychiatric testing</td><td headers="hd_h_m-sulfatase-def.T.surveillance_to_consid_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">PFT = pulmonary function test</p></div></dd></dl><dl class="bkr_refwrap"><dt>1. </dt><dd><div id="m-sulfatase-def.TF.5.1"><p class="no_margin">To screen for progressive hydrocephalus and/or cord compression</p></div></dd></dl><dl class="bkr_refwrap"><dt>2. </dt><dd><div id="m-sulfatase-def.TF.5.2"><p class="no_margin">To monitor bone health</p></div></dd></dl><dl class="bkr_refwrap"><dt>3. </dt><dd><div id="m-sulfatase-def.TF.5.3"><p class="no_margin">To monitor for cardiac hypertrophy, progressive valvular abnormalities, arrhythmia, and hypertension</p></div></dd></dl><dl class="bkr_refwrap"><dt>4. </dt><dd><div id="m-sulfatase-def.TF.5.4"><p class="no_margin">With special attention to the liver, gallbladder, and spleen</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobmsulfatasedefmolgenTA"><div id="m-sulfatase-def.molgen.TA" class="table"><h3><span class="label">Table A.</span></h3><div class="caption"><p>Multiple Sulfatase Deficiency: Genes and Databases</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK538937/table/m-sulfatase-def.molgen.TA/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__m-sulfatase-def.molgen.TA_lrgtbl__"><table class="no_bottom_margin"><tbody><tr><th id="hd_b_m-sulfatase-def.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">Gene</th><th id="hd_b_m-sulfatase-def.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">Chromosome Locus</th><th id="hd_b_m-sulfatase-def.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">Protein</th><th id="hd_b_m-sulfatase-def.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">Locus-Specific Databases</th><th id="hd_b_m-sulfatase-def.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">HGMD</th><th id="hd_b_m-sulfatase-def.molgen.TA_1_1_1_6" rowspan="1" colspan="1" style="vertical-align:top;">ClinVar</th></tr><tr><td headers="hd_b_m-sulfatase-def.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">
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<a href="/gene/285362" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=gene">
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<i>SUMF1</i>
|
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</a>
|
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</td><td headers="hd_b_m-sulfatase-def.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">
|
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<a href="https://www.ncbi.nlm.nih.gov/genome/gdv/?context=gene&acc=285362" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">3p26<wbr style="display:inline-block"></wbr>​.1</a>
|
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</td><td headers="hd_b_m-sulfatase-def.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">
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<a href="http://www.uniprot.org/uniprot/Q8NBK3" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Formylglycine-generating enzyme</a>
|
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</td><td headers="hd_b_m-sulfatase-def.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">
|
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<a href="http://databases.lovd.nl/shared/genes/SUMF1" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">SUMF1 database</a>
|
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</td><td headers="hd_b_m-sulfatase-def.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">
|
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<a href="http://www.hgmd.cf.ac.uk/ac/gene.php?gene=SUMF1" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">SUMF1</a>
|
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</td><td headers="hd_b_m-sulfatase-def.molgen.TA_1_1_1_6" rowspan="1" colspan="1" style="vertical-align:top;">
|
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<a href="https://www.ncbi.nlm.nih.gov/clinvar/?term=SUMF1[gene]" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">SUMF1</a>
|
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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 id="m-sulfatase-def.TFA.1"><p class="no_margin">Data are compiled from the following standard references: gene from
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<a href="http://www.genenames.org/index.html" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">HGNC</a>;
|
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chromosome locus from
|
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<a href="http://www.omim.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">OMIM</a>;
|
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protein from <a href="http://www.uniprot.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">UniProt</a>.
|
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For a description of databases (Locus Specific, HGMD, ClinVar) to which links are provided, click
|
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<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="figobmsulfatasedefmolgenTB"><div id="m-sulfatase-def.molgen.TB" class="table"><h3><span class="label">Table B.</span></h3><div class="caption"><p>OMIM Entries for Multiple Sulfatase Deficiency (<a href="/omim/272200,607939" 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/NBK538937/table/m-sulfatase-def.molgen.TB/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__m-sulfatase-def.molgen.TB_lrgtbl__"><table><tbody><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<a href="/omim/272200" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">272200</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MULTIPLE SULFATASE DEFICIENCY; MSD</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<a href="/omim/607939" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">607939</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">SULFATASE-MODIFYING FACTOR 1; SUMF1</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobmsulfatasedefTsumf1pathogenicvaria"><div id="m-sulfatase-def.T.sumf1_pathogenic_varia" class="table"><h3><span class="label">Table 6. </span></h3><div class="caption"><p><i>SUMF1</i> Pathogenic Variants Discussed in This <i>GeneReview</i></p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK538937/table/m-sulfatase-def.T.sumf1_pathogenic_varia/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__m-sulfatase-def.T.sumf1_pathogenic_varia_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_m-sulfatase-def.T.sumf1_pathogenic_varia_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">DNA Nucleotide Change</th><th id="hd_h_m-sulfatase-def.T.sumf1_pathogenic_varia_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Predicted Protein Change</th><th id="hd_h_m-sulfatase-def.T.sumf1_pathogenic_varia_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Reference Sequences</th></tr></thead><tbody><tr><td headers="hd_h_m-sulfatase-def.T.sumf1_pathogenic_varia_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">c.463T>C</td><td headers="hd_h_m-sulfatase-def.T.sumf1_pathogenic_varia_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Ser155Prp</td><td headers="hd_h_m-sulfatase-def.T.sumf1_pathogenic_varia_1_1_1_3" 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_182760.3" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NM_182760<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_877437.2" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NP_877437<wbr style="display:inline-block"></wbr>​.2</a>
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</td></tr><tr><td headers="hd_h_m-sulfatase-def.T.sumf1_pathogenic_varia_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">c.739G>C</td><td headers="hd_h_m-sulfatase-def.T.sumf1_pathogenic_varia_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Gly247Arg</td></tr><tr><td headers="hd_h_m-sulfatase-def.T.sumf1_pathogenic_varia_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">c.788G>T</td><td headers="hd_h_m-sulfatase-def.T.sumf1_pathogenic_varia_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Gly263Val</td></tr><tr><td headers="hd_h_m-sulfatase-def.T.sumf1_pathogenic_varia_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">c.836C>T</td><td headers="hd_h_m-sulfatase-def.T.sumf1_pathogenic_varia_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Arg279Val</td></tr><tr><td headers="hd_h_m-sulfatase-def.T.sumf1_pathogenic_varia_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">c.1033C>T</td><td headers="hd_h_m-sulfatase-def.T.sumf1_pathogenic_varia_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Arg345Cys</td></tr><tr><td headers="hd_h_m-sulfatase-def.T.sumf1_pathogenic_varia_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">c.1045C>T</td><td headers="hd_h_m-sulfatase-def.T.sumf1_pathogenic_varia_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Arg349Trp</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></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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