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  • Test code: 06175
  • 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 Mucopolysaccharidosis Type II (MPS II) Test

Test description

The Invitae Mucopolysaccharidosis Type II Test analyzes the IDS gene, which is associated with mucopolysaccharidosis type 2 (MPSII). This test is useful for the diagnosis of patients in whom MPS II deficiency is suspected due to clinical symptoms, biochemical findings, or abnormal newborn screening results.

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Primary panel (1 gene)
Add-on Clinically-overlapping Genes (4 genes)

Phenotypic features of MPS II can overlap with other MPSs and mucolipidosis type III a/b. Given the significant clinical overlap between these conditions, analyzing the genes associated with MPS I, MPS VII, mucolipidosis type III a/b and multiple sulfatase deficiency may be appropriate. These genes may be included at no additional charge.

GNPTAB GUSB IDUA SUMF1

Alternative tests to consider

For a broader analysis of mucopolysaccharidosis (MPS:

  • mucopolysaccharidosis type II (MPS II) – also known as Hunter syndrome

Mucopolysaccharridosis type II (MPSII, Hunter syndrome) is a progressive, multi-system disorder that is caused by a deficiency of iduronate-2-sulfatase, an enzyme that is necessary for the breakdown of dermatan sulfate and heparan sulfate. Affected males are normal at birth after uncomplicated pregnancies, but symptoms begin to develop around two years of age. Increased accumulation of mucopolysaccharides leads to characteristic facial features such as thickened lips, enlarged tongue, a full lower aspect of the face, depressed nasal bridge, thickened eyebrows, and frontal bossing. Patients also develop hepatosplenomegaly, frequent ear infections, and a thickening of the vocal cords and airway that leads to hoarseness and sleep apnea. Umbilical and inguinal hernias may also develop and may reappear after surgical correction. Patients may develop hearing loss, short stature, joint contractures, spinal stenosis, and dysostosis multiplex, which is characterized by oar-shaped ribs, gibbus deformity, abnormal vertebrae, shortened and thickened clavicles, and trident-shaped hands. Carpal tunnel syndrome may also develop in childhood. Affected males do not, however, get the typical corneal clouding that is characteristic of the other MPS syndromes.

MPSII is an X-linked disorder. Presentation is most commonly in early childhood. Affected males may have a range of phenotypic severity from severe progressive disease with intellectual disability and life expectancy reaching the second decade to a milder presentation where intellect is spared and patients can live into adulthood. Though MPSII is an X-linked condition, females have been reported with this syndrome—a rare result of skewed X inactivation, genomic rearrangements involving the X chromosome, and, in one occurrence (the product of a consanguineous mating), homozygous pathogenic variants.

Patients with MPSII will have low iduronate-2-sulfatase enzyme activity in leukocytes or dried blood spots. Patients may also show accumulation of dermatan and heparan sulfate in urine glycosaminoglycan analysis. Newer tandem mass spectrometry methods have greatly improved the sensitivity and specificity of urine glycosaminoglycan analysis.

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

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).

MPSII is inherited in an X-linked recessive manner.

MPSII is one of the more common mucopolysaccharidoses. The general prevalence for MPSII is estimated at 1 in 140,000–156,000.

  1. Yund, B, et al. Cognitive, medical, and neuroimaging characteristics of attenuated mucopolysaccharidosis type II. Mol. Genet. Metab. 2015; 114(2):170-7. PMID: 25541100
  2. Scarpa, M, et al. Mucopolysaccharidosis type II: European recommendations for the diagnosis and multidisciplinary management of a rare disease. Orphanet J Rare Dis. 2011; 6:72. PMID: 22059643
  3. Wang, RY, et al. Lysosomal storage diseases: diagnostic confirmation and management of presymptomatic individuals. Genet. Med. 2011; 13(5):457-84. PMID: 21502868
  4. Lonardo, F, et al. Mucopolysaccharidosis type II in a female patient with a reciprocal X;9 translocation and skewed X chromosome inactivation. Am. J. Med. Genet. A. 2014; 164A(10):2627-32. PMID: 25044788
  5. Johnson, BA, et al. Diagnosing lysosomal storage disorders: mucopolysaccharidosis type II. Curr Protoc Hum Genet. 2013; 79:Unit 17.14.. PMID: 24510650
  6. Shimada, T, et al. Novel heparan sulfate assay by using automated high-throughput mass spectrometry: Application to monitoring and screening for mucopolysaccharidoses. Mol. Genet. Metab. 2014; 113(1-2):92-9. PMID: 25092413
  7. Kumar, AB, et al. Tandem Mass Spectrometry Has a Larger Analytical Range than Fluorescence Assays of Lysosomal Enzymes: Application to Newborn Screening and Diagnosis of Mucopolysaccharidoses Types II, IVA, and VI. Clin. Chem. 2015; 61(11):1363-71. PMID: 26369786
  8. Tomanin, R, et al. Clinical efficacy of enzyme replacement therapy in paediatric Hunter patients, an independent study of 3.5 years. Orphanet J Rare Dis. 2014; 9:129. PMID: 25231261
  9. da, Silva, EM, et al. Enzyme replacement therapy with idursulfase for mucopolysaccharidosis type II (Hunter syndrome). Cochrane Database Syst Rev. 2014; 1:CD008185. PMID: 24399699
  10. Tanaka, A, et al. Long-term efficacy of hematopoietic stem cell transplantation on brain involvement in patients with mucopolysaccharidosis type II: a nationwide survey in Japan. Mol. Genet. Metab. 2012; 107(3):513-20. PMID: 23022072
  11. Scarpa, M. Mucopolysaccharidosis Type II. 2007 Nov 06. In: Pagon, RA, et al, editors. GeneReviews(®) (Internet). University of Washington, Seattle. PMID: 20301451
  12. Wraith JE. Inborn metabolic diseases: diagnosis and treatment. 5th ed. Heidelberg: Springer; 2012. Chapter 40, Mucopolysaccharidoses and oligosaccharidoses; p. 579–590.

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
GNPTAB NM_024312.4
GUSB NM_000181.3
IDS* NM_000202.6
IDUA NM_000203.4
SUMF1 NM_182760.3

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