• Test code: 06186
  • 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 I (MPS I) Test

Test description

The Invitae Mucopolysaccharidosis Type I Test analyzes the IDUA gene, which is associated with mucopolysaccharidosis type 1 (MPS I). This test is useful for the diagnosis of patients in whom MPS I 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 Lysosomal Storage Disorder Genes (5 genes)

Phenotypic features of MPS I can overlap with many other lysosomal storage diseases. Given the significant clinical similarity between Hunter and Sly syndromes, Mucolipidosis III a/b (aka pseudo-Hurler dystrophy), and multiple sulfatase deficiency, these genes can be included at no additional charge.


Alternative tests to consider

For a broader analysis of the genetics of mucopolysaccharidosis and lysosomal storage disorders:

  • mucopolysaccharidosis type 1 (MPS I)
    • severe and attenuated MPS I

MPS I is a clinically heterogeneous, progressive lysosomal storage disorder that is associated with a wide range of clinical manifestations of variable severity. Historically, three clinical subtypes have been described (Hurler, Hurler-Scheie, and Scheie syndromes); however, since it is now recognized that these conditions are all caused by the same gene, it is now described as a clinical spectrum. Affected individuals are described as having severe or attenuated MPS I. Severe MPS I usually manifests in infancy, whereas attenuated MPS I manifests later in childhood with milder features. Affected individuals often have no clinical signs at birth, but may present with inguinal or umbilical hernias which may recur after repair. Coarsening of the facial features, caused by accumulation of mucopolysaccharides, usually becomes apparent by early childhood in severe cases. MPS I is multi-systemic and additional clinical features which may develop as the condition progresses include hepatomegaly, cardiac defects, skeletal anomalies (gibbus deformity, dysostosis multiplex), arthropathy, short stature, hydrocephaly, and hearing loss. Ocular manifestations (corneal clouding, glaucoma, retinal degeneration) often result in loss of vision. Narrowing of the airway can lead to frequent upper respiratory infections and sleep apnea. Carpal tunnel syndrome may also develop in childhood. Many children experience alternating periods of constipation and diarrhea. Early psychomotor development may be normal, however individuals with severe MPS I usually show progressive intellectual disability. In comparison, intellect may be normal in attenuated MPS I.

Severe MPS I has a rapid progression, and affected individuals typically do not survive beyond childhood. Progression of attenuated MPS I is variable and individuals can survive into adolescence or into adulthood. Death most commonly occurs secondary to cardiorespiratory disease.

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

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.

For the clinical sensitivity of MPS II, please see the IDS clinical sensitivity table.

MPS I is inherited in an autosomal recessive manner.

MPS I is seen in all populations at a frequency of approximately 1:100,000 for the severe form and 1:500,000 for the attenuated form.

Any individual with a positive newborn screen for MPS I, deficient activity of the lysosomal enzyme α-L-iduronidase, high levels of urinary glycosaminoglycans, or a suspected diagnosis of MPS I based on clinical presentation, should be tested for MPS I. Clinical signs that may indicate testing include coarse facial features, early frequent upper-respiratory infections, inguinal or umbilical hernia, hepatosplenomegaly, characteristic skeletal findings (gibbus deformity, dysostosis multiplex), corneal clouding, developmental delay and hearing loss.

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 and 10 to 20 base pairs of adjacent intronic sequence on either side of the coding exons in the transcript listed below. In addition, the analysis covers the select non-coding variants specifically defined in the table below. Any variants that fall outside these regions are not analyzed. Any limitations in the analysis of these genes will be listed on the report. Contact client services with any questions.

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
ARSB NM_000046.3
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).