• 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

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.


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. Johnson, BA, et al. Diagnosing lysosomal storage disorders: mucopolysaccharidosis type II. Curr Protoc Hum Genet. 2013; 79:Unit 17.14.. PMID: 24510650
  2. 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
  3. 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
  4. 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
  5. Scarpa, M. Mucopolysaccharidosis Type II. 2007 Nov 06. In: Pagon, RA, et al, editors. GeneReviews(®) (Internet). University of Washington, Seattle. PMID: 20301451
  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. 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
  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. Wang, RY, et al. Lysosomal storage diseases: diagnostic confirmation and management of presymptomatic individuals. Genet. Med. 2011; 13(5):457-84. PMID: 21502868
  10. Wraith JE. Inborn metabolic diseases: diagnosis and treatment. 5th ed. Heidelberg: Springer; 2012. Chapter 40, Mucopolysaccharidoses and oligosaccharidoses; p. 579–590.
  11. Yund, B, et al. Cognitive, medical, and neuroimaging characteristics of attenuated mucopolysaccharidosis type II. Mol. Genet. Metab. 2015; 114(2):170-7. PMID: 25541100
  12. 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

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.

Our analysis detects most intragenic deletions and duplications at single exon resolution. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. If you are requesting the detection of a specific single-exon copy number variation, please contact Client Services before placing your order.

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).