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  • Test code: 06187
  • 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 III (MPS III) Panel

Test description

The Invitae Mucopolysaccharidosis Type III Panel analyzes four genes, which are associated with mucopolysaccharidosis type III (MPS III, or Sanfilippo syndrome). This test is useful for the diagnosis of patients in whom MPS III is suspected due to clinical symptoms or elevated urinary glycosaminoglycans (GAGs). Identification of disease-causing variants provide accurate risk assessment and carrier status for at-risk relatives.

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Primary panel (4 genes)
  • mucopolysaccharidosis type III (MPS III, Sanfilippo syndrome)
    • MPS IIIA
    • MPS IIIB
    • MPS IIIC
    • MPS IIID

MPS III is a lysosomal storage disorder due to enzyme deficiencies necessary to breakdown the glycosaminoglycan, heparan sulfate. Lysosomal accumulation of heparan sulfate results in deterioration and degeneration of tissues. Four distinct enzymes are involved in the degradation of heparan sulfate and reduced, or absent, activity of any one of these enzymes can cause MPS III. The four subtypes of MPS III are relatively clinically indistinguishable.

Clinically, MPS III is primarily characterized by central nervous system involvement and three phases of progressive neurologic deterioration. After a period of normal development, phase 1 is marked by an early childhood presentation of speech and psychomotor delays with or without behavioral problems. Phase 2 is characterized by a significant increase in behavioral issues, around 3-5 years of age, along with sleep disturbances and hyperactivity. Affected individuals may remain in this state for 5-10 years. The final phase is marked by a regression in behavioral problems accompanied by a significant decline in neurologic function that progresses to a vegetative state. Premature death frequently occurs in adolescence to early adulthood, but survival into the sixth decade has been reported in attenuated cases. Additional features frequently include hearing deficits, recurrent ear infections, diarrhea, and epilepsy. Somatic manifestations such as hepatomegaly, dysostosis multiplex, coarse facies and hypertrichosis are relatively mild compared to the other mucopolysaccharidoses. Treatment for MPS III is supportive as intravenous enzyme replacement therapies are unable to cross the blood-brain barrier. The efficacy of intrathecal enzyme replacement and gene therapy in MPS IIIA and B is being investigated in separate clinical trials.

Biochemical findings include significantly increased urinary glycosaminoglycan (GAG) excretion, specifically heparan sulfate.

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.

All forms of MPS III are inherited in an autosomal recessive pattern.

All forms of MPS III have a combined prevalence of 0.3 to 4.1 in 100,000 births.

Testing for MPS III is appropriate for any individual with any combination of clinical features consistent with a MPS III including: progressive developmental delay, autistic features, sleep disturbances and mildly coarse facial features.

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
GNS NM_002076.3
HGSNAT NM_152419.2
NAGLU NM_000263.3
SGSH NM_000199.3