Mucopolysaccharidosis Type VI / Maroteaux-Lamy Syndrome via the ARSB Gene
Summary and Pricing 
Test Method
Sequencing and CNV Detection via NextGen Sequencing using PG-Select Capture Probes| Test Code | Test Copy Genes | Test CPT Code | Gene CPT Codes Copy CPT Code | Base Price | |
|---|---|---|---|---|---|
| 7865 | ARSB | 81479 | 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.
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 (Neufeld and Muenzer 2001; Coutinho et al. 2012 ). See also the National MPS Society at www.mpssociety.org.
MPS VI, also called Moroteaux-Lamy syndrome, is caused by deficiency in lysosomal arylsulfatase B and subsequent accumulation and excessive urinary excretion of dermatan sulfate. It is distinguished from other MPS by normal mental development, although physical and visual abnormalities may affect psychomotor performance.
In the most severe forms of the syndrome, several symptoms may be apparent at birth and include enlarged head, deformed chest, and umbilical hernia. As the disease progresses, additional symptoms arise and include coarse facial features, corneal clouding, joint stiffness, claw-hand deformities, carpal tunnel, hepatosplenomegaly, hirsutism, and cardiomyopathy. Death usually occurs by the third decade of life as the result of heart failure (Neufeld and Muenzer 2001).
The mild form of MPS VI is characterized by later age of onset, usually after the second decade of life, slow progression and compressive myelopathy as the result of thickening of dura mater and subsequent spinal cord compression (Young et al. 1980; Wald et al. 1984).
MPS VI occurs in diverse ethnic and geographical populations (Kantaputra et al. 2014), with an estimated prevalence of 0.16 in 100,000 live births (Orphanet).
Genetics
MPS VI is an autosomal recessive disease that results from pathogenic variants in the ARSB gene (Wicker et al. 1991). About 160 variants have been reported in patients from various ethnic and geographic populations. Most causative variants are missense, some of which affect amino acids that are not well conserved. Large pathogenic deletions appear to be rare (Human Gene Mutation Database).
Although some variants, when in the homozygous state, result in severe phenotypes (Brands et al. 2013), other variants result in a wide range of phenotypes (Isbrandt et al. 1994), making genotype-phenotype correlations difficult.
The ARSB gene encodes the arylsulfatase B enzyme, which catalyzes the hydrolysis of dermatan sulfate.
Clinical Sensitivity - Sequencing with CNV PG-Select
Clinical sensitivity is unknown as no studies assessing clinical sensitivity are known at this time. Using Sanger sequencing, pathogenic variants in the ARSB gene were identified in over 97% of the mutated alleles in patients biochemically proven to have MPS VI (Jurecka et al. 2012).
Pathogenic large deletions in the ARSB gene appear to be rare. To date, only two such deletions have been listed in the Human Gene Mutation Database (Arlt et al. 1994; Villani et al. 2010).
Testing Strategy
This test provides full coverage of all coding exons of the ARSB 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 VI in patients with clinical features and radiological findings suggestive of MPS, increased urinary dermatan sulfate excretion, and reduced arylsulfatase B enzyme activity; and identification of asymptomatic heterozygous carriers.
Confirmation of the diagnosis of MPS VI in patients with clinical features and radiological findings suggestive of MPS, increased urinary dermatan sulfate excretion, and reduced arylsulfatase B enzyme activity; and identification of asymptomatic heterozygous carriers.
Gene
| Official Gene Symbol | OMIM ID |
|---|---|
| ARSB | 611542 |
| Inheritance | Abbreviation |
|---|---|
| Autosomal Dominant | AD |
| Autosomal Recessive | AR |
| X-Linked | XL |
| Mitochondrial | MT |
Disease
| Name | Inheritance | OMIM ID |
|---|---|---|
| Mucopolysaccharidosis Type VI | AR | 253200 |
Citations
- Arlt G, Brooks DA, Isbrandt D, Hopwood JJ, Bielicki J, Bradford TM, Bindloss-Petherbridge CA, Figura K von, Peters C. 1994. Juvenile form of mucopolysaccharidosis VI (Maroteaux-Lamy syndrome). A C-terminal extension causes instability but increases catalytic efficiency of arylsulfatase B. J. Biol. Chem. 269: 9638–9643. PubMed ID: 8144552
- Brands MM, Hoogeveen-Westerveld M, Kroos MA, Nobel W, Ruijter GJ, Ozkan L, Plug I, Grinberg D, Vilageliu L, Halley DJ, Ploeg AT van der, Reuser AJ. 2013. Mucopolysaccharidosis type VI phenotypes-genotypes and antibody response to galsulfase. Orphanet J Rare Dis 8: 51. PubMed ID: 23557332
- Coutinho MF, Lacerda L, Alves S. 2012. Glycosaminoglycan Storage Disorders: A Review. Biochemistry Research International 2012: 1–16. PubMed ID: 22013531
- Human Gene Mutation Database.
- Isbrandt D, Arlt G, Brooks DA, Hopwood JJ, Figura K von, Peters C. 1994. Mucopolysaccharidosis VI (Maroteaux-Lamy syndrome): six unique arylsulfatase B gene alleles causing variable disease phenotypes. Am J Hum Genet 54: 454–463. PubMed ID: 8116615
- Jurecka A, Piotrowska E, Cimbalistiene L, Gusina N, Sobczynska A, Czartoryska B, Czerska K, Õunap K, Wegrzyn G, Tylki-Szymanska A. 2012. Molecular analysis of mucopolysaccharidosis type VI in Poland, Belarus, Lithuania and Estonia. Mol. Genet. Metab. 105: 237–243. PubMed ID: 22133300
- Kantaputra PN, Kayserili H, Guven Y, Kantaputra W, Balci MC, Tanpaiboon P, Tananuvat N, Uttarilli A, Dalal A. 2014. Clinical manifestations of 17 patients affected with mucopolysaccharidosis type VI and eight novel ARSB mutations. Am. J. Med. Genet. A 164A: 1443–1453. PubMed ID: 24677745
- National MPS Society
- Neufeld EF, Muenzer J. 2001. The Mucoploysaccharidoses. 136: 3421-3452.
- Orphanet
- Villani GRD, Grosso M, Pontarelli G, Chierchia A, Sessa R, Sibilio M, Parenti G, Natale P Di. 2010. Large deletion involving exon 5 of the arylsulfatase B gene caused apparent homozygosity in a mucopolysaccharidosis type VI patient. Genet Test Mol Biomarkers 14: 113–120. PubMed ID: 20143913
- Wald SL, Schmidek HH. 1984. Compressive myelopathy associated with type VI mucopolysaccharidosis (Maroteaux-Lamy syndrome). Neurosurgery 14: 83–88. PubMed ID: 6420724
- Wicker G, Prill V, Brooks D, Gibson G, Hopwood J, Figura K von, Peters C. 1991. Mucopolysaccharidosis VI (Maroteaux-Lamy syndrome). An intermediate clinical phenotype caused by substitution of valine for glycine at position 137 of arylsulfatase B. J. Biol. Chem. 266: 21386–21391. PubMed ID: 1718978
- Young R, Kleinman G, Ojemann RG, Kolodny E, Davis K, Halperin J, Zalneraitis E, DeLong GR. 1980. Compressive myelopathy in Maroteaux-Lamy syndrome: clinical and pathological findings. Ann. Neurol. 8: 336–340. PubMed ID: 6776877
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
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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