Test Catalog

Test Id : LSDGP

Lysosomal Storage Disease Gene Panel, Varies

Useful For
Suggests clinical disorders or settings where the test may be helpful

Follow up for abnormal biochemical results and confirmation of suspected lysosomal storage disease (LSD)

 

Establishing a molecular diagnosis for patients with LSD

 

Identifying variants within genes known to be associated with LSD, allowing for predictive testing of at-risk family members

Genetics Test Information
Provides information that may help with selection of the correct genetic test or proper submission of the test request

This test utilizes next-generation sequencing to detect single nucleotide and copy number variants in 56 genes associated with lysosomal storage disease: AGA, ARSA, ARSB, ASAH1, ATP13A2, CHIT1, CLN3, CLN5, CLN6, CLN8, CTNS, CTSA, CTSD, CTSF, CTSK, DNAJC5, FUCA1, GAA, GALC, GALNS, GBA, GFAP, GLA, GLB1, GM2A, GNPTAB, GNPTG, GNS, GRN, GUSB, HEXA, HEXB, HGSNAT, HYAL1, IDS, IDUA, KCTD7, LAMP2, LIPA, MAN2B1, MANBA, MCOLN1, MFSD8, NAGA, NAGLU, NEU1, NPC1, NPC2, PANK2, PPT1, PSAP, SGSH, SLC17A5, SMPD1, SUMF1, TPP1. See Targeted Genes and Methodology Details for Lysosomal Storage Disease Gene Panel and Method Description for additional details.

 

Identification of a pathogenic variant may assist with diagnosis, prognosis, clinical management, familial screening, and genetic counseling for lysosomal storage disease.

 

Additional first-tier testing may be considered/recommended. For more information see Ordering Guidance and Testing Algorithm sections. 

Reflex Tests
Lists tests that may or may not be performed, at an additional charge, depending on the result and interpretation of the initial tests.

Test Id Reporting Name Available Separately Always Performed
FIBR Fibroblast Culture Yes No
CRYOB Cryopreserve for Biochem Studies No No

Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

See Lysosomal Storage Disorders Diagnostic Algorithm, Part 2 in Special Instructions. If skin biopsy is received, fibroblast culture and cryopreservation for biochemical studies will be added at an additional charge.

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Method Name
A short description of the method used to perform the test

Sequence Capture and Targeted Next-Generation Sequencing followed by Polymerase Chain Reaction (PCR) and Sanger Sequencing.

NY State Available
Indicates the status of NY State approval and if the test is orderable for NY State clients.

Yes

Reporting Name
Lists a shorter or abbreviated version of the Published Name for a test

LSD Gene Panel

Aliases
Lists additional common names for a test, as an aid in searching

Alexander disease

Alpha-mannosidase deficiency

Aspartylglucosaminuria (AGU)

Beta-mannosidosis

Chitotriosidase deficiency (with Gaucher 1)

Cystinosis

Fabry disease

Farber lipogranulomatosis

Fucosidosis

Galactosialidosis

Gaucher Disease

Glycogen Storage Disease Type IIB-Danon Disease

GM2-gangliosidosis, AB variant

Krabbe disease

LSD

Lysosomal acid lipase deficiency/Wolman disease

Lysosomal acid phosphatase deficiency (ACPHD)

Metachromatic leukodystrophy

Mucolipidosis II, and III

Mucolipidosis III gamma

Mucolipidosis type IV

Mucopolysaccharidosis type I (Hurler/Scheie)

Mucopolysaccharidosis type II Hunter disease

Mucopolysaccharidosis Type IIIA Sanfilippo

Mucopolysaccharidosis Type IIIB

Mucopolysaccharidosis type IIIC (Sanfilippo)

Mucopolysaccharidosis type IIID Sanfilippo D

Mucopolysaccharidosis Type IVA Morquio A

Mucopolysaccharidosis type IVB-Morquio B

Mucopolysaccharidosis type iX: Hyaluronidase deficiency

Mucopolysaccharidosis Type VI Maroteaux-Lamy

Mucopolysaccharidosis type VII Sly

Multiple sulfatase deficiency

NCL

Next Gen Sequencing Test

Niemann-Pick type A/B

Niemann-Pick type C1 and C2

Niemann-Pick type C1 and C3

Pompe disease-glycogen storage disease type II

Prosaposin Deficiency

Sandhoff disease

Schindler disease

Sialic acid storage disease

Sialidosis

Tay-Sachs disease

Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

See Lysosomal Storage Disorders Diagnostic Algorithm, Part 2 in Special Instructions. If skin biopsy is received, fibroblast culture and cryopreservation for biochemical studies will be added at an additional charge.

Specimen Type
Describes the specimen type validated for testing

Varies

Ordering Guidance

For neuronal ceroid lipofuscinosis, first-tier biochemical testing is available for the 2 most common types of enzyme deficiency; see TPPTL / Tripeptidyl Peptidase 1 and Palmitoyl-Protein Thioesterase 1, Leukocytes.

 

Testing for the 15 neuronal ceroid lipofuscinosis genes is available separately; see NCLGP / Neuronal Ceroid Lipofuscinosis (Batten Disease) Gene Panel, Varies.

 

Customization of this panel and single gene analysis for any gene present on this panel is available. For more information see CGPH / Custom Gene Panel, Hereditary, Next-Generation Sequencing, Varies.

Shipping Instructions

Specimen preferred to arrive within 96 hours of collection.

Specimen Required
Defines the optimal specimen required to perform the test and the preferred volume to complete testing

Patient Preparation: A previous bone marrow transplant from an allogenic donor will interfere with testing. Call 800-533-1710 for instructions for testing patients who have received a bone marrow transplant.

 

Submit only 1 of the following specimens:

 

Specimen Type: Whole blood

Container/Tube:

Preferred: Lavender top (EDTA) or yellow top (ACD)

Acceptable: Any anticoagulant

Specimen Volume: 3 mL

Collection Instructions:

1. Invert several times to mix blood.

2. Send specimen in original tube. Do not aliquot.

Specimen Stability Information: Ambient (preferred)/Refrigerated

 

Specimen Type: Skin biopsy

Supplies: Fibroblast Biopsy Transport Media (T115)

Container/Tube: Sterile container with any standard cell culture media (e.g., minimal essential media, RPMI 1640). The solution should be supplemented with 1% penicillin and streptomycin.

Specimen Volume: 4-mm punch

Specimen Stability Information: Refrigerated (preferred)/Ambient

 

Specimen Type: Cultured fibroblast

Container/Tube: T-25 flask

Specimen Volume: 2 Flasks

Collection Instructions: Submit confluent cultured fibroblast cells from a skin biopsy from another laboratory. Cultured cells from a prenatal specimen will not be accepted.

Specimen Stability Information: Ambient (preferred)/Refrigerated (<24 hours)

Additional Information: A separate culture charge will be assessed under FIBR / Fibroblast Culture, Tissue. An additional 4 weeks is required to culture fibroblasts before genetic testing can occur.

 

Specimen Type: Blood spot

Supplies: Card-Blood Spot Collection (Filter Paper) (T493)

Container/Tube:

Preferred: Collection card (Whatman Protein Saver 903 Paper)

Acceptable: PerkinElmer 226 (formerly Ahlstrom 226) filter paper, or blood spot collection card

Specimen Volume: 5 Blood spots

Collection Instructions:

1. An alternative blood collection option for a patient older than 1 year of age is fingerstick. See Dried Blood Spot Collection Tutorial for how to collect blood spots: https://vimeo.com/508490782 

2. Let blood dry on the filter paper at ambient temperature in a horizontal position for a minimum of 3 hours.

3. Do not expose specimen to heat or direct sunlight.

4. Do not stack wet specimens.

5. Keep specimen dry

Specimen Stability Information: Ambient (preferred)/Refrigerated

Additional Information:

1. For collection instructions, see Blood Spot Collection Instructions in Special Instructions.

2. For collection instructions in Spanish, see Blood Spot Collection Card-Spanish Instructions (T777) in Special Instructions.

3. For collection instructions in Chinese, see Blood Spot Collection Card-Chinese Instructions (T800) in Special Instructions.

4. Due to lower concentration of DNA yielded from blood spot, it is possible that additional specimen may be required to complete testing.

 

Specimen Type: Saliva

Patient Preparation: Patient should not eat, drink, smoke, or chew gum 30 minutes prior to collection.

Supplies: Saliva Swab Collection Kit (T786)

Specimen Volume: 1 Swab

Collection Instructions: Collect and send specimen per kit instructions.

Specimen Stability Information: Ambient 30 days

Additional Information: Due to lower concentration of DNA yielded from saliva, it is possible that additional specimen may be required to complete testing.

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Forms

1. New York Clients-Informed consent is required. Document on the request form or electronic order that a copy is on file. The following documents are available in Special Instructions:

-Informed Consent for Genetic Testing  (T576)

-Informed Consent for Genetic Testing (Spanish) (T826)

2. Molecular Genetics: Biochemical Disorders Patient Information (T527) in Special Instructions

Specimen Minimum Volume
Defines the amount of sample necessary to provide a clinically relevant result as determined by the Testing Laboratory

See Specimen Required

Reject Due To
Identifies specimen types and conditions that may cause the specimen to be rejected

All specimens will be evaluated at Mayo Clinic Laboratories for test suitability.

Specimen Stability Information
Provides a description of the temperatures required to transport a specimen to the performing laboratory, alternate acceptable temperatures are also included

Specimen Type Temperature Time Special Container
Varies Varies (preferred)

Useful For
Suggests clinical disorders or settings where the test may be helpful

Follow up for abnormal biochemical results and confirmation of suspected lysosomal storage disease (LSD)

 

Establishing a molecular diagnosis for patients with LSD

 

Identifying variants within genes known to be associated with LSD, allowing for predictive testing of at-risk family members

Genetics Test Information
Provides information that may help with selection of the correct genetic test or proper submission of the test request

This test utilizes next-generation sequencing to detect single nucleotide and copy number variants in 56 genes associated with lysosomal storage disease: AGA, ARSA, ARSB, ASAH1, ATP13A2, CHIT1, CLN3, CLN5, CLN6, CLN8, CTNS, CTSA, CTSD, CTSF, CTSK, DNAJC5, FUCA1, GAA, GALC, GALNS, GBA, GFAP, GLA, GLB1, GM2A, GNPTAB, GNPTG, GNS, GRN, GUSB, HEXA, HEXB, HGSNAT, HYAL1, IDS, IDUA, KCTD7, LAMP2, LIPA, MAN2B1, MANBA, MCOLN1, MFSD8, NAGA, NAGLU, NEU1, NPC1, NPC2, PANK2, PPT1, PSAP, SGSH, SLC17A5, SMPD1, SUMF1, TPP1. See Targeted Genes and Methodology Details for Lysosomal Storage Disease Gene Panel and Method Description for additional details.

 

Identification of a pathogenic variant may assist with diagnosis, prognosis, clinical management, familial screening, and genetic counseling for lysosomal storage disease.

 

Additional first-tier testing may be considered/recommended. For more information see Ordering Guidance and Testing Algorithm sections. 

Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

See Lysosomal Storage Disorders Diagnostic Algorithm, Part 2 in Special Instructions. If skin biopsy is received, fibroblast culture and cryopreservation for biochemical studies will be added at an additional charge.

Clinical Information
Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Lysosomal storage diseases (LSD) encompass a group of over 40 inherited biochemical diseases in which genetic variants cause defective lysosomal functioning. Lysosomes perform catabolic functions for cells, which is accomplished through activity of various proteins such as lysosomal enzymes, transport proteins, and other proteins. Functional deficits in these proteins cause an accumulation of substrates in cells leading to progressive organ dysfunction.

 

This leads to variable clinical features that can affect the cardiovascular, neurological, ocular, and skeletal systems, among others. Clinical features are dependent on the amount and location of the substrate accumulation but may include the following: characteristic facial features (coarse features), hepatomegaly, deafness, vision loss, abnormal skeletal findings, hydrops fetalis, ataxia, hypotonia, developmental delay/regression, and intellectual disability. Age of onset is variable, with symptoms presenting from the prenatal period to adulthood, but generally LSD are progressive and cause significant morbidity and mortality with a decreased lifespan. Enzyme replacement therapy and oral substrate inhibitors are therapeutic options for some LSD.

 

LSD are inherited in an autosomal recessive manner with the exception of Hunter, Fabry, and Danon diseases, which are X-linked. There are founder variants associated with particular LSD in the Ashkenazi Jewish and Finnish populations, leading to an increased carrier frequency for some. Overall, the prevalence of LSD is estimated at 1 in 7000 to 1 in 8000.

 

Neuronal ceroid lipofuscinoses (NCL) are a subset of LSD that involve defective cellular processing of lipids. NCL are clinically characterized by epilepsy, intellectual and motor decline, and blindness. Electron microscopy typically shows a characteristic accumulation of granular osmophilic deposits (GROD), curvilinear profiles (CVB), or fingerprint profiles (FP). Enzymatic testing may show deficiency in palmitoyl-protein thioesterase 1 (PPT1), tripeptidyl-peptidase 1 (TPP1), or cathepsin D (CTSD). Currently there are at least 14 genetically distinct forms.

 

Age of onset and clinical features can be variable, from congenital to adult onset. NCL is typically inherited in an autosomal recessive manner, although one adult onset form (ANCL; DNAJC5 gene) has been shown to be autosomal dominant.

 

This panel includes sequencing of 43 genes related to various LSD, as well as 15 genes specific to NCL.

 

Alterations in various genes on this panel have also been associated with Parkinson disease or Lewy body disease. These alterations are not reported for individuals younger than 18 years of age but are available upon request.

Reference Values
Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

An interpretive report will be provided.

Interpretation
Provides information to assist in interpretation of the test results

All detected alterations are evaluated according to American College of Medical Genetics and Genomics (ACMG) recommendations.(1) Variants are classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance.

Cautions
Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

Clinical Correlations:

Test results should be interpreted in context of clinical findings, family history, and other laboratory data. Misinterpretation of results may occur if the information provided is inaccurate or incomplete.

 

If testing was performed because of a clinically significant family history, it is often useful to first test an affected family member. Detection of at least one reportable variant in an affected family member would allow for more informative testing of at-risk individuals.

 

To discuss the availability of additional testing options, for assistance in general test selection, or for assistance in the interpretation of these results, contact the Mayo Clinic Laboratory genetic counselors at 800-533-1710.

 

Technical Limitations:

Next-generation sequencing may not detect all types of genomic variants. In rare cases, false-negative or false-positive results may occur. The depth of coverage may be variable for some target regions; assay performance below the minimum acceptable criteria or for failed regions will be noted. Given these limitations, negative results do not rule out the diagnosis of a genetic disorder. If a specific clinical disorder is suspected, evaluation by alternative methods can be considered.

 

There may be regions of genes that cannot be effectively evaluated by sequencing or deletion and duplication analysis as a result of technical limitations of the assay, including regions of homology, high guanine-cytosine (GC) content, and repetitive sequences. Confirmation of select reportable variants will be performed by alternate methodologies based on internal laboratory criteria.

 

This test is validated to detect 95% of deletions up to 75 base pairs (bp) and insertions up to 47 bp. Insertions/deletions (indels) of 40 or more bp, including mobile element insertions, may be less reliably detected than smaller indels.

 

Deletion/Duplication Analysis: This analysis targets single and multi-exon deletions/duplications; however, in some instances single exon resolution cannot be achieved due to isolated reduction in sequence coverage or inherent genomic complexity. Balanced structural rearrangements (such as translocations and inversions) may not be detected.

 

This test is not designed to detect low levels of mosaicism or to differentiate between somatic and germline variants. If there is a possibility that any detected variant is somatic, additional testing may be necessary to clarify the significance of results.

 

Genes may be added or removed based on updated clinical relevance. See Targeted Genes and Methodology Details for Lysosomal Storage Disease Gene Panel for the most up to date list of genes included in this test.

 

For detailed information regarding gene specific performance and technical limitations, see Technical Limitations section or contact a laboratory genetic counselor.

 

If the patient has had an allogeneic hematopoietic stem cell transplant or a recent heterologous blood transfusion, results may be inaccurate due to the presence of donor DNA. Call Mayo Clinic Laboratories for instructions for testing patients who have received a bone marrow transplant.

 

Reclassification of Variants:

At this time, it is not standard practice for the laboratory to systematically review previously classified variants on a regular basis. The laboratory encourages health care providers to contact the laboratory at any time to learn how the status of a particular variant may have changed over time.

 

Variant Evaluation:

Evaluation and categorization of variants is performed using published American College of Medical Genetics and Genomics (ACMG) and Association for Molecular Pathology (AMP) recommendations as a guideline.(1) Other gene specific guidelines may also be considered. Variants are classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance. Variants classified as benign or likely benign are not reported.

 

Multiple in silico evaluation tools may be used to assist in the interpretation of these results. The accuracy of predictions made by in silico evaluation tools is highly dependent upon the data available for a given gene, and periodic updates to these tools may cause predictions to change over time. Results from in silico evaluation tools should be interpreted with caution and professional clinical judgment.

Clinical Reference
Recommendations for in-depth reading of a clinical nature

1. Richards S, Aziz N, Bale S, et al: Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015 May;17(5):405-424

2. Wang RY, Bodamer OA, Watson MS, Wilcox WR; ACMG Work Group on Diagnostic Confirmation of Lysosomal Storage Diseases: Lysosomal storage diseases: Diagnostic confirmation and management of presymptomatic individuals. Genet Med. 2011;13(5):457-484

3. Parenti G, Andria G, Ballabio A: Lysosomal storage diseases: from pathophysiology to therapy. Ann Rev Med. 2015;66:471-486

4. Filocamo, M. Morrone A: Lysosomal storage disorders: Molecular basis and laboratory testing. Hum Genomics. 2011;5:156-169

5. Coutinho MF, Alves S: From rare to common and back again: 60 years of lysosomal dysfunction. Mol Genet Metab. 2016 Feb;117(2):53-65

6. Robak LA, Jansen IE, van Rooij J, et al: Excessive burden of lysosomal storage disorder gene variants in Parkinson's disease. Brain. 2017 Dec 1;140(12):3191-3203

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Method Description
Describes how the test is performed and provides a method-specific reference

Next-generation sequencing (NGS) and/or Sanger sequencing is performed to test for the presence of variants in coding regions and intron/exon boundaries of the genes analyzed, as well as some other regions that have known pathogenic variants. The human genome reference GRCh37/hg19 build was used for sequence read alignment. At least 99% of the bases are covered at a read depth over 30X. Sensitivity is estimated at above 99% for single nucleotide variants, above 94% for insertions/deletions (indels) less than 40 base pairs (bp), above 95% for deletions up to 75 bp and insertions up to 47 bp. NGS and/or a polymerase chain reaction (PCR)-based quantitative method is performed to test for the presence of deletions and duplications in the genes analyzed. See Targeted Genes and Methodology Details for Lysosomal Storage Disease Gene Panel for details regarding the targeted genes analyzed.

 

There may be regions of genes that cannot be effectively evaluated by sequencing or deletion and duplication analysis as a result of technical limitations of the assay, including regions of homology, high guanine-cytosine (GC) content, and repetitive sequences. See Targeted Genes and Methodology Details for Lysosomal Storage Disease Gene Panel for details regarding the specific gene regions not routinely covered.(Unpublished Mayo method)

 

Genes analyzed: AGA, ARSA, ARSB, ASAH1, ATP13A2, CHIT1, CLN3, CLN5, CLN6, CLN8, CTNS, CTSA, CTSD, CTSF, CTSK, DNAJC5, FUCA1, GAA, GALC, GALNS, GBA, GFAP, GLA, GLB1, GM2A, GNPTAB, GNPTG, GNS, GRN, GUSB, HEXA, HEXB, HGSNAT, HYAL1, IDS, IDUA, KCTD7, LAMP2, LIPA, MAN2B1, MANBA, MCOLN1, MFSD8, NAGA, NAGLU, NEU1, NPC1, NPC2, PANK2, PPT1, PSAP, SGSH, SLC17A5, SMPD1, SUMF1, TPP1

PDF Report
Indicates whether the report includes an additional document with charts, images or other enriched information

Supplemental

Day(s) Performed
Outlines the days the test is performed. This field reflects the day that the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time before the test is performed. Some tests are listed as continuously performed, which means that assays are performed multiple times during the day.

Varies

Report Available
The interval of time (receipt of sample at Mayo Clinic Laboratories to results available) taking into account standard setup days and weekends. The first day is the time that it typically takes for a result to be available. The last day is the time it might take, accounting for any necessary repeated testing.

4 to 6 weeks

Specimen Retention Time
Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded

Whole Blood: 2 weeks (if available); Extracted DNA: 3 months; Blood spots: 1 month; Saliva: 1 month

Performing Laboratory Location
Indicates the location of the laboratory that performs the test

Rochester

Fees
Several factors determine the fee charged to perform a test. Contact your U.S. or International Regional Manager for information about establishing a fee schedule or to learn more about resources to optimize test selection.

  • Authorized users can sign in to Test Prices for detailed fee information.
  • Clients without access to Test Prices can contact Customer Service 24 hours a day, seven days a week.
  • Prospective clients should contact their Regional Manager. For assistance, contact Customer Service.

Test Classification
Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR) product.

This test was developed, and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the US Food and Drug Administration.

CPT Code Information
Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Clinic Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.

CPT codes are provided by the performing laboratory.

81443

88233-Tissue culture, skin, solid tissue biopsy (if appropriate)

88240-Cryopreservation (if appropriate)

LOINC® Information
Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the order and results codes of this test. LOINC values are provided by the performing laboratory.

Test Id Test Order Name Order LOINC Value
LSDGP LSD Gene Panel In Process
Result Id Test Result Name Result LOINC Value
Applies only to results expressed in units of measure originally reported by the performing laboratory. These values do not apply to results that are converted to other units of measure.
608536 Test Description 62364-5
608537 Specimen 31208-2
608538 Source 31208-2
608539 Result Summary 50397-9
608540 Result 82939-0
608541 Interpretation 69047-9
608542 Resources 99622-3
608543 Additional Information 48767-8
608544 Method 85069-3
608545 Genes Analyzed 48018-6
608546 Disclaimer 62364-5
608547 Released By 18771-6

Test Setup Resources

Setup Files
Test setup information contains test file definition details to support order and result interfacing between Mayo Clinic Laboratories and your Laboratory Information System.

Excel | Create a PDF

Sample Reports
Normal and Abnormal sample reports are provided as references for report appearance.

Normal Reports | Abnormal Reports

SI Sample Reports
International System (SI) of Unit reports are provided for a limited number of tests. These reports are intended for international account use and are only available through MayoLINK accounts that have been defined to receive them.

SI Normal Reports | SI Abnormal Reports