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  • Test code: 06171
  • 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 Lysosomal Storage Disorders Newborn Screening Panel

Test description

The Invitae Lysosomal Storage Disorders Newborn Screening Panel analyzes 6 genes associated with lysosomal storage disorders (LSDs) that are now screened for in several United States newborn screening (NBS) programs. The specific conditions screened varies by state and is determined by each state.

This panel may be appropriate for infants in whom a LSD is suspected due to abnormal newborn screening results. Additionally, any infant with reduced enzymatic activity in a lysosomal enzyme should undergo variant analysis as lysosomal enzymes have known pseudodeficiency alleles. Pseudodeficiency alleles result in decreased enzyme activity but do NOT cause clinical disease.

Genetic testing of these genes may confirm a diagnosis, help guide treatment and management decisions and provide genetic counseling. Identification of disease-causing variants provides accurate risk assessment and carrier status of at-risk relatives.

Please note this panel does not include testing for Gaucher disease.

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Primary panel (6 genes)
Gene Disorders
GAA Pompe Disease
GALC Krabbe Disease
GLA Fabry Disease
IDS Mucopolysaccharidosis type II (MPS II, also known as Hunter syndrome)
IDUA Mucopolysaccharidosis type I (MPS I, also known as Hurler, Hurler-Scheie or Scheie syndome)
SMPD1 Niemann-Pick Disease type A and B

Please note this panel does not include testing for Gaucher disease.

Lysosomal storage disorders are a group of metabolic disorders characterized by an abnormal buildup of waste products in the lysosomes due to the absence, or deficiency, of a specific lysosomal enzyme. These disorders can affect many different organs and systems, including the heart, skeleton, skin, kidneys, liver, and central nervous system. Common symptoms include progressive intellectual delay, cardiac abnormalities, seizures, vision and hearing loss, organomegaly, and skeletal abnormalities, among others.

The severity of a lysosomal storage disorder can vary greatly depending on the level of residual enzymatic activity. If some enzyme activity is present, symptoms are usually less severe and manifest later in life. If enzymatic activity is significantly reduced or absent, symptoms tend to be more severe and manifest in infancy, or even in the prenatal period.

Often, early medical intervention can help prevent irreversible damage and improve the outcomes of patients who are affected with these disorders. Treatment with enzyme replacement or substrate reduction therapies is available for some LSDs and is actively being developed for other LSDs.

The majority of lysosomal storage diseases are inherited in an autosomal recessive manner. Fabry disease and Hunter syndrome are inherited in an X-linked manner.

Individually, lysosomal storage disorders are rare disorders. However, the total estimated incidence of all lysosomal storage disorders is about 1 in 2,500.

  • The incidence of Pompe disease is approximately 1 in 40,000.
  • The incidence of Krabbe disease is approximately 1 in 100,000.
  • The incidence of Fabry disease is approximately 1 in 40,000.
  • The combined incidence of Hurler syndrome, Hurler-Scheie syndrome, and Scheie syndrome is approximately 1 in 100,000.
  • The incidence of Hunter syndrome is approximately 1 in 100,000.
  • The incidence of Niemann-Pick disease types A and B is approximately 1 in 250,000.

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
GAA* NM_000152.3
GALC* NM_000153.3
GLA* NM_000169.2
IDS* NM_000202.6
IDUA NM_000203.4
SMPD1 NM_000543.4

GAA: Analysis includes the promoter variant NM_000152.3:c.-32-13T>G as well as the common exon 18 deletion.
GALC: Analysis includes the large (30 kb) deletion for Krabbe Disease.
GLA: Analysis includes the intronic variant NM_000169.2:c.IVS4+919G>A.
IDS: Detection of complex rearrangements not offered (PMID: 7633410, 20301451).