Mucopolysaccharidosis Type IIIB / Sanfilippo Syndrome B via the NAGLU 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
7757 NAGLU 81479 81479,81479 $640 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
7757NAGLU81479 81479(x2) $640 Order Options and Pricing

Pricing Comments

This test is also offered via our exome backbone with CNV detection (click here). The exome-based test may be higher priced, but permits reflex to the entire exome or to any other set of clinically relevant genes.

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

Turnaround Time

18 days on average for standard orders or 13 days 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.

EMAIL CONTACTS

Genetic Counselors

Geneticist

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 IIIB is caused by deficiency of the alpha-N-acetyl-glucosaminidase.

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

Genetics

MPS IIIB is an autosomal recessive disease caused by pathogenic variants in the NAGLU gene (Zhao et al. 1996). About 150 pathogenic variants have been reported in patients from various ethnic and geographical populations. They include missense, nonsense, splicing, and small insertions or deletions mutations (Human Mutation Gene Database). Large deletions that cannot be detected by Sanger sequencing appear to be rare. Only one such deletion is reported (Champion et al. 2010).

There are no clear genotype-phenotype correlations because most pathogenic variants are private or occur with low frequencies (Yogalingam and Hopwood 2001; Wijburg et al. 2013). Nonetheless, it appears that most causative mutations in the NAGLU gene lead to severe MPS III (Zhao et al.1998).

The NAGLU gene encodes alpha-N-acetyl-glucosaminidase, 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 NAGLU gene were identified in all analyzed patients who have clinical features suggestive of MPS, elevated urinary heparan sulfate, and low levels of alpha-N-acetyl-glucosaminidase activity in the plasma (Zhao et al. 1998).

Large pathogenic deletions in NAGLU appear to be rare (Human Gene Mutation Database). Only one such deletion is reported (Champion et al. 2010).

Testing Strategy

This test provides full coverage of all coding exons of the NAGLU 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 IIIB in patients with clinical features and radiological findings suggestive of MPS III, increased urinary heparan sulfate excretion, and reduced alpha-N-acetylglucosaminidase activity; and identification of asymptomatic heterozygous carriers.

Gene

Official Gene Symbol OMIM ID
NAGLU 609701
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Mucopolysaccharidosis, MPS-III-B AR 252920

Related Test

Name
Mucopolysaccharidosis Type III Panel

Citations

  • Champion KJ, Basehore MJ, Wood T, Destrée A, Vannuffel P, Maystadt I. 2010. Identification and characterization of a novel homozygous deletion in the alpha-N-acetylglucosaminidase gene in a patient with Sanfilippo type B syndrome (mucopolysaccharidosis IIIB). Mol. Genet. Metab. 100: 51–56. PubMed ID: 20138557
  • Human Gene Mutation Database (Bio-base).
  • Neufeld EF, Muenzer J. 2001. The Mucoploysaccharidoses. 136: 3421-3452.
  • Orphanet
  • 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
  • Zhao HG, Aronovich EL, Whitley CB. 1998. Genotype-phenotype correspondence in Sanfilippo syndrome type B. The American Journal of Human Genetics 62: 53–63. PubMed ID: 9443875
  • Zhao HG, Li HH, Bach G, Schmidtchen A, Neufeld EF. 1996. The molecular basis of Sanfilippo syndrome type B. Proceedings of the National Academy of Sciences 93: 6101–6105. PubMed ID: 8650226

Ordering/Specimens

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


Specimen Types

Specimen Requirements and Shipping Details

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ORDER OPTIONS

View Ordering Instructions

1) Select Test Method (Backbone)


1) Select Test Type


2) Select Additional Test Options

STAT and Prenatal Test Options are not available with Patient Plus.

No Additional Test Options are available for this test.

Note: acceptable specimen types are whole blood and DNA from whole blood only.
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