Invitae Mucopolysaccharidosis Type 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)


Mucopolysaccharidosis type II (MPS II, 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.

Greater than 99% of patients with clinical and biochemical features of MPS II will have a pathogenic variant in the IDS gene.

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, and select noncoding variants. Our assay provides a Q30 quality-adjusted mean coverage depth of 350x (50x minimum, or supplemented with additional analysis). Variants classified as pathogenic or likely pathogenic are confirmed with orthogonal methods, except individual variants that have high quality scores and previously validated in at least ten unrelated samples.

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
IDS NM_000202.6