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Mucopolysaccharidosis Type IIID / Sanfilippo Syndrome D via the GNS Gene

Summary and Pricing

Test Method

Sequencing and CNV Detection via NextGen Sequencing using PG-Select Capture Probes
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
GNS 81479 81479,81479 $990
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
7185GNS81479 81479,81479 $990 Order Options and Pricing

Pricing Comments

Testing run on PG-select capture probes includes CNV analysis for the gene(s) on the panel but does not permit the optional add on of exome-wide CNV analysis. Any of the NGS platforms allow reflex to other clinically relevant genes, up to whole exome or whole genome sequencing depending upon the base platform selected for the initial test.

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

This test is also offered via a custom panel (click here) on our exome or genome backbone which permits the optional add on of exome-wide CNV or genome-wide SV analysis.

Turnaround Time

3 weeks on average for standard orders or 2 weeks on average for STAT orders.

Please note: Once the testing process begins, an Estimated Report Date (ERD) range will be displayed in the portal. This is the most accurate prediction of when your report will be complete and may differ from the average TAT published on our website. About 85% of our tests will be reported within or before the ERD range. We will notify you of significant delays or holds which will impact the ERD. Learn more about turnaround times here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.


Genetic Counselors


  • Jana Paderova, PhD

Clinical Features and Genetics

Clinical Features

The mucopolysaccharidoses (MPS) are a group of inherited disorders caused by defects in lysosomal enzymes responsible for the stepwise degradation of glycosaminoglycans (GAGs). Each enzyme deficiency results in progressive storage of distinct GAGs in multiple organ systems and subsequent abnormalities. Although MPS share several symptoms, including physical and mental developmental abnormalities, they may differ even within the same enzyme deficiency. Seven clinically distinct types can be recognized (Types I, II, III, IV, VI, VII, and IX). Based on the biochemical and genetic defects, MPS III and IV are further divided in four and two subtypes, respectively. Deficiencies in eleven enzymes have been implicated in the various MPS.

Mucopolysaccharidosis Type III, also known as Sanfilippo syndrome is caused by deficiency in any of four lysosomal enzymes involved in the stepwise degradation of heparan sulfate. Enzyme deficiencies result in progressive storage of heparan sulfate primarily in the central nervous system, leading to severe neurodegeneration and developmental delay. MPSIII is classified into four subtypes (MPS IIIA to D) on the basis of the specific enzyme deficiency. MPS IIID is caused by deficiency of the lysosomal N-acetylglucosamine 6-sulfatase.

Clinically, MPS III is distinguished from the other MPS by a severe cognitive and neurological impairment; and mild somatic signs. The characteristic features are similar in all four subtypes, although MPS IIIA is usually associated with an earlier age of onset and a faster progression compared to the other MPS. Symptoms appear during childhood and death usually occurs by the second or third decade of life. Symptoms typically begin with episodes of hyperactivity and aggressive behavior and progress to severe behavioral and sleep disturbances, speech difficulties, hearing and visual defects, and mental retardation. Somatic involvement is variable. Symptoms include mildly coarse facial features, recurrent ear and respiratory infections, scoliosis, hip dysplasia, carpal tunnel syndrome and cardiac valve disease (Neufeld and Muenzer 2001; Wijburg et al. 2013). MPS IIID is the rarest subtype. Only 26 families with the history of MPS IIID have been reported to date (Valstar et al. 2010).

MPS III occurs in diverse ethnic and geographical populations with an estimated prevalence of 0.87:100,000 per live births (www.orpha.net).


MPS IIID is inherited with an autosomal recessive manner; it is caused by pathogenic variants in the GNS gene (Beesley et al. 2003; Mok et al. 2003). A total of about 25 pathogenic variants are reported in patients from various ethnic and geographical populations. Most variants are predicted to result in protein truncation and include nonsense, splicing, small insertions or deletions and large deletions. Only three missense variants are reported to date. They occur within the sulphatase domain and affect highly conserved amino acids (Valstar et al. 2010; Human Mutation Gene Database).

As in the case of the other MP III subtypes, there are no clear genotype-phenotype correlations because most pathogenic variants are private or occur with low frequencies (Yogalingam and Hopwood 2001). In addition, severity and clinical course vary even among sibs with GNS causative mutations (Valstar et al. 2010). Genetic and environmental modifying factors, including intrauterine environment, are suspected to contribute to the phenotypic presentation (Jansen et al. 2007).

The GNS gene encodes N-acetylglucosamine-6-sulfatase, one of four lysosomal enzymes involved in the stepwise degradation of heparan sulfate.

Clinical Sensitivity - Sequencing with CNV PG-Select

Using Sanger sequencing, pathogenic variants in the GNS gene were identified in about 85% of the alleles in patients with clinical features suggestive of MPS, elevated urinary heparan sulfate, and low levels of N-acetylglucosamine-6-sulfatase in leukocytes or cultured skin fibroblasts. Large deletions were identified in all the remaining alleles (Valstar et al. 2010).

Large pathogenic deletions were found in about 15% of the mutated alleles (Valstar et al. 2010). They represent about 18 % of the known GNS causative variants (Human Gene Mutation Database).

Testing Strategy

This test provides full coverage of all coding exons of the GNS gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.

Indications for Test

Confirmation of the diagnosis of MPS IIID in patients with clinical features and radiological findings suggestive of MPS III, increased urinary heparan sulfate excretion, and reduced N-acetylglucosamine 6-sulfatase activity; and identification of asymptomatic heterozygous carriers.


Official Gene Symbol OMIM ID
GNS 607664
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


Name Inheritance OMIM ID
Mucopolysaccharidosis, MPS-III-D AR 252940

Related Test

Mucopolysaccharidosis Type III Panel


  • Beesley CE, Burke D, Jackson M, Vellodi A, Winchester BG, Young EP. 2003. Sanfilippo syndrome type D: identification of the first mutation in the N-acetylglucosamine-6-sulphatase gene. Journal of medical genetics 40: 192–194. PubMed ID: 12624138
  • Human Gene Mutation Database (Bio-base).
  • Jansen AC, Cao H, Kaplan P, Silver K, Leonard G, Meirleir L De, Lissens W, Liebaers I, Veilleux M, Andermann F, others. 2007. Sanfilippo syndrome type D: natural history and identification of 3 novel mutations in the GNS Gene. Archives of neurology 64: 1629–1634. PubMed ID: 17998446
  • Mok A, Cao H, Hegele RA. 2003. Genomic basis of mucopolysaccharidosis type IIID (MIM 252940) revealed by sequencing of GNS encoding N-acetylglucosamine-6-sulfatase. Genomics 81: 1–5. PubMed ID: 12573255
  • Neufeld EF, Muenzer J. 2001. The Mucoploysaccharidoses. 136: 3421-3452.
  • Orphanet
  • Valstar MJ, Bertoli-Avella AM, Wessels MW, Ruijter GJG, Graaf B de, Olmer R, Elfferich P, Neijs S, Kariminejad R, Suheyl Ezgü F, Tokatli A, Czartoryska B, et al. 2010. Mucopolysaccharidosis type IIID: 12 new patients and 15 novel mutations. Human Mutation n/a–n/a. PubMed ID: 20232353
  • Wijburg FA, Wegrzyn G, Burton BK, Tylki-Szymanska A. 2013. Mucopolysaccharidosis type III (Sanfilippo syndrome) and misdiagnosis of idiopathic developmental delay, attention deficit/hyperactivity disorder or autism spectrum disorder. Acta Paediatrica 102: 462–470. PubMed ID: 23336697
  • Yogalingam G, Hopwood JJ. 2001. Molecular genetics of mucopolysaccharidosis type IIIA and IIIB: Diagnostic, clinical, and biological implications. Hum. Mutat. 18: 264–281. PubMed ID: 11668611


Ordering Options

We offer several options when ordering sequencing tests. For more information on these options, see our Ordering Instructions page. To view available options, click on the Order Options button within the test description.

myPrevent - Online Ordering

  • The test can be added to your online orders in the Summary and Pricing section.
  • Once the test has been added log in to myPrevent to fill out an online requisition form.
  • PGnome sequencing panels can be ordered via the myPrevent portal only at this time.

Requisition Form

  • A completed requisition form must accompany all specimens.
  • Billing information along with specimen and shipping instructions are within the requisition form.
  • All testing must be ordered by a qualified healthcare provider.

For Requisition Forms, visit our Forms page

If ordering a Duo or Trio test, the proband and all comparator samples are required to initiate testing. If we do not receive all required samples for the test ordered within 21 days, we will convert the order to the most effective testing strategy with the samples available. Prior authorization and/or billing in place may be impacted by a change in test code.

Specimen Types

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