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  • Test code: 06188
  • 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 IV (MPS IV) Panel

Test description

The Invitae mucopolysaccharidosis type IV (MPS IV, also known as Morquio syndrome) panel analyzes the GALNS and GLB1 genes. MPS IV is a lysosomal storage disease caused by accumulation of keratan sulfate and chondroitin-6-sulfate in various tissues. Pathogenic variants in GALNS and GLB1 lead to MPS IVA and MPS IVB, respectively.

This test is indicated for any individual in whom MPS IV is suspected based on clinical or laboratory findings. Enzyme replacement therapy (ERT) may be available for some affected individuals, so early diagnosis is critical in potentially mitigating clinical symptoms.

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Primary panel (2 genes)
Add-on Multiple Sulfatase Deficiency Gene (1 gene)

Multiple sulfatase deficiency is a condition causing deficiencies of all of the lysosomal sulfatases, including N-acetylgalactosamine 6-sulfatase (GALNS). If prior enzyme analysis demonstrated abnormal GALNS activity but no other sulfatases were tested, it may be appropriate to analyze the SUMF1 gene to rule out multiple sulfatase deficiency. This gene can be added at no additional charge.

SUMF1

Alternative tests to consider

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

  • mucopolysaccharidosis type IV (MPS IV, Morquio syndrome)
    • mucopolysaccharidosis type IVA (Morquio Syndrome Type A)
    • mucopolysaccharidosis type IVB (Morquio Syndrome Type B)

MPS IV, also known as Morquio syndrome, is a childhood-onset lysosomal storage disease caused by an enzyme deficiency of N-acetylgalactosamine 6-sulfatase or B-galactosidase. This enzyme is necessary for the breakdown of keratan sulfate and chondroitin-6-sulfate; which are found predominantly in the bone and cornea. The two subtypes (MPS IVA and MPS IVB caused by pathogenic variants in the GALNS and GLB1 genes, respectively) have identical clinical presentation and can only be distinguished by biochemical or molecular genetic testing.

Affected infants typically do not display any features at birth, but in childhood develop severe skeletal and joint abnormalities. Features include short-trunk dwarfism, short neck, joint hypermobility, respiratory disease, cardiac disease, impaired vision with corneal clouding, hearing loss, dental abnormalities, hepatomegaly, and elevated urinary keratan sulfate. Intellect is typically normal with normal neurological development, however, spinal cord compression may lead to neurologic compromise. Severity and rate of progression are highly variable; life expectancy ranges from 10 years to almost normal.

For individuals with clinical features of MPS IV, pathogenic sequence variants and deletion/duplication events in the GALNS or GLB1 gene are identified in nearly all cases.

GALNS (MPS IVA) accounts for over 95% of MPS IV cases, while GLB1 (MPS IVB) accounts for fewer than 5% of cases.

MPS IV is inherited in an autosomal recessive manner.

Prevalence data for this rare disease is limited. Prevalence estimates for MPS IVA range from 1 in 71,000 to 1 in 926,000. Prevalence estimates for MPS IVB range from 1 in 250,000 to less than 1 in 1,000,000.

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
GALNS NM_000512.4
GLB1 NM_000404.2
SUMF1 NM_182760.3