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  • Test code: 06200
  • 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 Oligosaccharidoses Panel

Test description

The Invitae Oligosaccharidoses panel analyzes up to 23 genes associated with oligosaccharidosis.

This panel may be appropriate for individuals with signs and symptoms of an oligosaccharidosis such as non-immune fetal hydrops, coarse facial features, progressive intellectual disability, hepatosplenomegaly, cardiomyopathy, angiokeratomas, cherry red spots on ophthalmologic evaluation and skeletal dysplasia. Additionally, this panel may be appropriate for those in whom an oligosaccharidosis is suspected due to biochemical findings. Genetic testing of these genes may confirm a diagnosis and help guide management decisions.

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Primary panel (8 genes)

AGA CTSA CTSK FUCA1 MAN2B1 MANBA NAGA SLC17A5

Add-on Mucolipidosis and Mucopolysaccharidosis Genes (15 genes)

The phenotypic features of the oligosaccharidoses can overlap with the mucopolysaccharidoses (MPS) and certain mucolipidoses, and making them difficult to distinguish clinically. Given the significant clinical overlap, analyzing the genes associated with these disorders may be appropriate. These genes may be included at no additional charge.

ARSB GALNS GLB1 GNPTAB GNPTG GNS GUSB HGSNAT HYAL1 IDS IDUA MCOLN1 NAGLU NEU1 SGSH

  • aspartylglucosaminuria (AGA)
  • alpha-mannosidosis (MAN2B1)
  • beta-mannosidosis (MANBA)
  • galactosialidosis (CTSA)
  • free sialic acid storage disease (SLC17A5)
  • fucosidosis (FUCA1)
  • pycnodysostosis (CTSK)
  • Schindler disease (NAGA)

The oligosaccharidoses are a constellation of diseases typically caused by individual lysosomal enzyme deficiencies involved in the stepwise breakdown of complex sugar side chains on glycoproteins (sugar and protein molecules). The majority of proteins in the body are glycosylated and these short sugar chains (oligosaccharides) are sequentially broken down during protein degradation. Deficiencies in any one of the enzymes involved in oligosaccharide breakdown leads to a metabolic block and accumulation of undigested oligosaccharides within the lysosomes. Free sialic acid storage disorders result from a defective lysosomal membrane transport protein that causes sialic acid to be sequestered within the lysosome. Progressive accumulation of oligosaccharides or sialic acid in multiple tissues leads to organ dysfunction and an oligosaccharidosis.

There is phenotypic variability amongst and within the oligosaccharidoses, but in general, clinical features of the oligosaccharidoses are similar those observed the mucopolysaccharidoses (MPSs). Affected individuals are typically asymptomatic at birth, although more severe cases may present with hydrops fetalis. Common features include progressive somatic involvement which may include any of the following features: coarse facies, skeletal dysplasia, hepatosplenomegaly, cardiac disease, cherry red spot on ophthalmologic exam, corneal clouding, deafness, hydrocephalus, progressive psychomotor delay and/or seizures. Additionally, some conditions present with an immunodeficiency or angiokeratomas. There is a clinical spectrum within each oligosaccharidosis ranging from a severe, early onset disorder to a milder, attenuated form. Reduced life expectancy is observed in virtually all of the oligosaccharidoses.

Biochemical abnormalities of the oligosaccharidoses include elevated urinary oligosaccharides with normal urinary glycosaminoglycans. Additionally, enzymatic activity specific to each disorder will be reduced.

Treatment for the oligosaccharidoses is supportive, although hematopoietic stem cell transplant (HCST) has been repeatedly used to treat alpha-mannosidosis. HCST has also been tried in other oligosaccharidoses.

The clinical sensitivity of this test is not known at this time.

The oligosaccharidoses are autosomal recessively inherited.

The overall prevalence of the oligosaccharidoses is not known as these conditions are exceedingly rare.

Aspartylglucosaminuria is the most commonly encountered oligosaccharidosis and has a high prevalence in Finland due to a common founder variant in the AGA gene, c.488G>C (p.Cys163Ser). The estimated incidence of aspartylglucosaminuria in the Finnish population is 1.7–5/100.000 live births.

Free sialic storage disease also has a high carrier frequency in northeastern Finland due to a pathogenic founder variant in SLC17A5 c.115C>T (p.Arg39Cys). The carrier frequency is estimated at 1:100 in this region, but the overall incidence of free sialic storage disease remains rare.

This test is appropriate for any individual with normal urinary GAG screening and any combination of clinical features consistent with an oligosaccharidosis including: coarse facial features, skeletal deformities, progressive mental retardation, hepatosplenomegaly, cardiomyopathy, angiokeratomas, recurrent ear and respiratory infections and or corneal clouding.

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
AGA NM_000027.3
ARSB NM_000046.3
CTSA NM_000308.3
CTSK NM_000396.3
FUCA1 NM_000147.4
GALNS NM_000512.4
GLB1 NM_000404.2
GNPTAB NM_024312.4
GNPTG NM_032520.4
GNS NM_002076.3
GUSB NM_000181.3
HGSNAT NM_152419.2
HYAL1 NM_153281.1
IDS* NM_000202.6
IDUA NM_000203.4
MAN2B1 NM_000528.3
MANBA NM_005908.3
MCOLN1 NM_020533.2
NAGA NM_000262.2
NAGLU NM_000263.3
NEU1 NM_000434.3
SGSH NM_000199.3
SLC17A5 NM_012434.4

IDS: Detection of complex rearrangements not offered (PMID: 7633410, 20301451).