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  • Test code: 06185
  • Turnaround time:
    10–21 calendar days (14 days on average)
  • Preferred specimen:
    3mL whole blood in a purple-top tube
  • Alternate specimens:
    DNA or saliva/assisted saliva
  • Sample requirements
  • Request a sample kit
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Invitae Comprehensive Mucopolysaccharidoses (MPS) Panel

Test description

The Invitae Comprehensive Mucopolysaccharidoses (MPS) Panel analyzes genes associated with mucopolysaccharidoses. This panel may be appropriate for individuals with signs and symptoms of a mucopolysaccharidosis such as coarse facial features, progressive cognitive disability, inguinal and/or umbilical hernias, hepatosplenomegaly, cardiac valve dysfunction, recurrent ear and respiratory infections, corneal clouding and skeletal deformities. Additionally, this panel may be appropriate for those in whom a MPS condition is suspected due biochemical findings or abnormal newborn screening results. Genetic testing of these genes may confirm a diagnosis and help guide treatment and management decisions.

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Primary panel (11 genes)

ARSB GALNS GLB1 GNS GUSB HGSNAT HYAL1 IDS IDUA NAGLU SGSH

Add-on Mucolipidosis and Oligosaccharidoses Genes (12 genes)

Phenotypic features of the mucopolysaccharidoses can overlap with certain mucolipidoses and oligosaccharidoses. Given the significant clinical overlap, analyzing the genes associated with these disorders may be appropriate. These genes may be included at no additional charge.

AGA CTSA CTSK FUCA1 GNPTAB GNPTG MAN2B1 MANBA MCOLN1 NAGA NEU1 SLC17A5

  • Mucopolysaccharidoses (MPS)
    • MPS I (Hurler syndrome)
    • MPS II (Hunter syndrome)
    • MPS III (Sanfilipo syndrome)
    • MPS IV (Morquio syndrome)
    • MPS VI (Maroteaux Lamy)
    • MPS VII (Sly syndrome)
    • MPS IX (Natowicz syndrome)

The mucopolysaccharidoses are a constellation of diseases caused by the deficiency of a specific lysosomal enzyme involved in the breakdown of complex sugar and protein molecules known as glycosaminoglycans (GAGs, previously called mucopolysaccharides). Specifically, the breakdown of one or more of the following GAGs is disrupted in each MPS: chondroitin sulfate (CS), dermatan sulfate (DS), heparan sulfate (HS), keratan sulfate (KS) and/or hyaluronan. Consequently, these substances accumulate in the lysosomes of various tissues resulting in deterioration and degeneration of multiple organs. There is phenotypic variability amongst and within the MPSs, but in general, extensive somatic involvement affecting the heart, lungs, bones, joints and gastrointestinal systems is observed in most MPSs and central nervous system involvement is seen in in types I, II, III and VII. There is a clinical spectrum within each MPS ranging from severe, early onset forms to milder, attenuated forms. Reduced life expectancy is observed in virtually all of the MPSs.

Treatment options, including hematopoietic stem-cell transplant and enzyme replacement therapy, are available for some forms of MPS. Early diagnosis may help slow disease progression and alleviate some symptoms.

Abnormal biochemical studies may include increased urinary GAG levels and reduced enzymatic activity of the enzyme specific to each MPS.

  • MPS I: For patients with clinical symptoms of MPS I, sequence variants in the gene IDUA are identified in 95%-97% of patients. Deletions/duplications in this gene are rare.
  • MPS II: Pathogenic variants in the IDS gene are the only known cause of mucopolysaccharidosis type II (PMID: 25345092). Among individuals with a confirmed clinical diagnosis of MPS II, 82% have sequence variants and 9% have exonic deletions/duplications, which are both detected in this assay. Another 9% of individuals have complex structural rearrangements that are not identified in this assay (PMID: 20301451).
  • MPS III: For individuals with a clinical diagnosis of MPS III approximately 60% will have a pathogenic variant in the SGSH gene, 30% in NAGLU, 4% in HGSNAT and 6% in GNS.
  • MPS IV: GALNS is the only gene known to be associated with MPS IV. However, due to the rarity of this condition, the percent of MPS IV attributed to pathogenic variants in GALNS is currently unknown.
  • MPS VI: ARSB is the only gene known to be associated with MPS VI. However, due to the rarity of this condition, the percent of MPS VI attributed to pathogenic variants in ARSB is currently unknown.
  • MPS VII: GUSB is the only gene known to be associated with MPS VII. However, due to the rarity of this condition, the percent of MPS VII attributed to pathogenic variants in GUSB is currently unknown.
  • MPS IX: HYAL1 is the only gene known to be associated with MPS IX. However, due to the rarity of this condition, the percent of MPS IX attributed to pathogenic variants in HYAL1 is currently unknown.

The MPSs are inherited in an autosomal recessive fashion, except for MPSII. MPSII is X-linked.

Collectively the MPSs have an overall incidence of greater than 1:25,000 births.

Individual incidence figures for the different forms of MPS are listed here:

MPS type Incidence
MPS I 1:100,00 for the severe form and 1:500,000 in the attenuated form
MPS II 1:100,00-1:170,000 male births
MPS III 0.3 to 4.1 : 100,000 births (all forms of MPS III)
MPS IV MPS IVA 1:71,00 – 179,000
MPS1B 1:250,00 – 1,000,000
MPS VI 1:46,261 births in Turkey to 1:1,505,160 in Sweden
MPS VII 1:345,000 – 2,100,000
MPS IX unknown

This test is appropriate for any individual with any combination of clinical features consistent with a MPS including: coarse facial features, skeletal deformities, progressive mental retardation, inguinal and umbilical hernias, hepatosplenomegaly, recurrent ear and respiratory infections and or corneal clouding.

  1. Cho, SY, et al. An overview of Korean patients with mucopolysaccharidosis and collaboration through the Asia Pacific MPS Network. Intractable Rare Dis Res. 2014; 3(3):79-86. PMID: 25364648
  2. Tomatsu, S, et al. Therapies for the bone in mucopolysaccharidoses. Mol. Genet. Metab. 2015; 114(2):94-109. PMID: 25537451
  3. Cimaz, R, La, Torre, F. Mucopolysaccharidoses. Curr Rheumatol Rep. 2014; 16(1):389. PMID: 24264718
  4. Muenzer, J. Overview of the mucopolysaccharidoses. Rheumatology (Oxford). 2011; 50 Suppl 5:v4-12. PMID: 22210669
  5. Scarpa, M. Mucopolysaccharidosis Type II. 2007 Nov 06. In: Pagon, RA, et al, editors. GeneReviews(®) (Internet). University of Washington, Seattle. PMID: 20301451
  6. Clarke, LA. Mucopolysaccharidosis Type I. 2002 Oct 31. In: Pagon, RA, et al, editors. GeneReviews(®) (Internet). University of Washington, Seattle. PMID: 20301341
  7. Andrade, F, et al. Sanfilippo syndrome: Overall review. Pediatr Int. 2015; 57(3):331-8. PMID: 25851924
  8. Leadley, RM, et al. A systematic review of the prevalence of Morquio A syndrome: challenges for study reporting in rare diseases. Orphanet J Rare Dis. 2014; 9:173. PMID: 25404155
  9. Hendriksz, CJ, et al. International guidelines for the management and treatment of Morquio A syndrome. Am. J. Med. Genet. A. 2015; 167A(1):11-25. PMID: 25346323
  10. Caciotti, A, et al. GM1 gangliosidosis and Morquio B disease: an update on genetic alterations and clinical findings. Biochim. Biophys. Acta. 2011; 1812(7):782-90. PMID: 21497194
  11. Regier, DS, Tifft, CJ. GLB1-Related Disorders. 2013 Oct 17. In: Pagon, RA, et al, editors. GeneReviews(®) (Internet). University of Washington, Seattle. PMID: 24156116
  12. Vairo, F, et al. Diagnostic and treatment strategies in mucopolysaccharidosis VI. Appl Clin Genet. 2015; 8:245-55. PMID: 26586959
  13. Tomatsu, S, et al. Newborn screening and diagnosis of mucopolysaccharidoses. Mol. Genet. Metab. 2013; 110(1-2):42-53. PMID: 23860310

Assay and technical information

Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).

Our sequence analysis covers clinically important regions of each gene, including coding exons, +/- 10 base pairs of adjacent intronic sequence in the transcript listed below. In addition, analysis covers the select non-coding variants specifically defined in the table below. Any variants that fall outside these regions are not analyzed. Any specific limitations in the analysis of these genes are also listed in the table below.

Based on validation study results, this assay achieves >99% analytical sensitivity and specificity for single nucleotide variants, insertions and deletions <15bp in length, and exon-level deletions and duplications. Invitae's methods also detect insertions and deletions larger than 15bp but smaller than a full exon but sensitivity for these may be marginally reduced. Invitae’s deletion/duplication analysis determines copy number at a single exon resolution at virtually all targeted exons. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. Certain types of variants, such as structural rearrangements (e.g. inversions, gene conversion events, translocations, etc.) or variants embedded in sequence with complex architecture (e.g. short tandem repeats or segmental duplications), may not be detected. Additionally, it may not be possible to fully resolve certain details about variants, such as mosaicism, phasing, or mapping ambiguity. Unless explicitly guaranteed, sequence changes in the promoter, non-coding exons, and other non-coding regions are not covered by this assay. Please consult the test definition on our website for details regarding regions or types of variants that are covered or excluded for this test. This report reflects the analysis of an extracted genomic DNA sample. In very rare cases, (circulating hematolymphoid neoplasm, bone marrow transplant, recent blood transfusion) the analyzed DNA may not represent the patient's constitutional genome.

Gene Transcript reference Sequencing analysis Deletion/Duplication analysis
AGA NM_000027.3
ARSB NM_000046.3
CTSA NM_000308.3
CTSK NM_000396.3
FUCA1 NM_000147.4
GALNS NM_000512.4
GLB1 NM_000404.2
GNPTAB NM_024312.4
GNPTG NM_032520.4
GNS NM_002076.3
GUSB NM_000181.3
HGSNAT NM_152419.2
HYAL1 NM_153281.1
IDS* NM_000202.6
IDUA NM_000203.4
MAN2B1 NM_000528.3
MANBA NM_005908.3
MCOLN1 NM_020533.2
NAGA NM_000262.2
NAGLU NM_000263.3
NEU1 NM_000434.3
SGSH NM_000199.3
SLC17A5 NM_012434.4

IDS: Detection of complex rearrangements not offered (PMID: 7633410, 20301451).