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Test ID LSDGP Lysosomal Storage Disease Gene Panel, 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


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.


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

Useful For

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

Testing Algorithm

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.

Method Name

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

Reporting Name

LSD Gene Panel

Specimen Type

Varies

Specimen Minimum Volume

See Specimen Required

Specimen Stability Information

Specimen Type Temperature Time Special Container
Varies Varies

Clinical Information

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

An interpretive report will be provided.

Interpretation

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.

Clinical Reference

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

Test Classification

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

81443

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

88240-Cryopreservation (if appropriate)

LOINC Code Information

Test ID Test Order Name Order LOINC Value
LSDGP LSD Gene Panel In Process

 

Result ID Test Result Name Result LOINC Value
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

Day(s) Performed

Varies

Report Available

4 to 6 weeks

Reflex Tests

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