Test Catalog

Test ID: LSDP    
Lysosomal Storage Disease Panel by Next-Generation Sequencing, 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)


Identifying mutations 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 includes next-generation sequencing and supplemental Sanger sequencing to evaluate the genes on this panel.


Risk alleles for Parkinson disease with no known enzyme reduction or lysosomal storage disease association will only be reported in patients older than age 18 unless otherwise requested.


See Targeted Genes Interrogated by Lysosomal Storage Disease Panel in Special Instructions for details regarding the targeted genes identified by this test.

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

See clinical information for recommended first-tier biochemical testing.


If skin biopsy is received, fibroblast culture will be added and charged separately.


For prenatal specimens only: If amniotic fluid (nonconfluent cultured cells) is received, amniotic fluid culture/genetic test will be added and charged separately. If chorionic villus specimen (nonconfluent cultured cells) is received, fibroblast culture for genetic test will be added and charged separately. For any prenatal specimen that is received, maternal cell contamination studies will be added.

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

Lysosomal storage diseases (LSDs) encompass a group of over 40 inherited biochemical diseases in which genetic mutations 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 LSDs are progressive and cause significant morbidity and mortality with a decreased lifespan. Enzyme replacement therapy and oral substrate inhibitors are therapeutic options for some LSDs.



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


Neuronal ceroid lipofuscinoses (NCLs) are a subset of lysosomal storage diseases that involve defective cellular processing of lipids. NCLs 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.


First-tier biochemical testing is available for the 2 most common types of enzyme deficiency resulting in NCL: TPPTL / Tripeptidyl Peptidase 1 (TPP1) and Palmitoyl-Protein Thioesterase 1 (PPT1), Leukocytes; and TPPTF / Tripeptidyl Peptidase 1 (TPP1) and Palmitoyl-Protein Thioesterase 1 (PPT1), Fibroblasts.

This panel includes sequencing of 43 genes related to various LSDs, as well as 15 genes specific to neuronal ceroid lipofuscinosis, for a total of 58 genes.


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.


See Targeted Genes Interrogated by Lysosomal Storage Disease Panel in Special Instructions for details regarding the targeted genes identified by this test.


Note: Testing for the 15 neuronal ceroid lipofuscinosis genes is also available separately; see NCLP / Neuronal Ceroid Lipofuscinosis (NCL, Batten Disease) Panel by Next-Generation Sequencing.

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 recommendations.(1) Variants are classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance.


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 predictions made by these tools may change over time. Results from in silico evaluation tools should be interpreted with caution and professional clinical judgment.

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

Clinical Correlations:

Some individuals who have involvement of 1 or more of the genes on the panel may have a mutation that is not identified by the methods performed (eg, promoter mutations, deep intronic mutations, large genomic deletions). The absence of a mutation, therefore, does not eliminate the possibility of a lysosomal storage disease (LSD).


For predictive testing of asymptomatic individuals, it is important to first document the presence of a gene mutation in an affected family member.


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


Technical Limitations:

In some cases, DNA variants of undetermined significance may be identified. Due to the limitations of next-generation sequencing, we can detect 90% of insertions and deletions up to 28 bases and 38 bases, respectively. If a diagnosis of 1 of the syndromes on this panel is still suspected, consider full gene sequencing using traditional Sanger methods.


Rare polymorphisms exist that could lead to false-negative or false-positive results. If results obtained do not match the clinical findings, additional testing should be considered.


Evaluation Tools:

Multiple in-silico evaluation tools were used to assist in the interpretation of these results. These tools are updated regularly; therefore, changes to these algorithms may result in different predictions for a given alteration. Additionally, the predictability of these tools for the determination of pathogenicity is currently not validated.


Unless reported or predicted to cause disease, alterations found deep in the intron or alterations that do not result in an amino acid substitution are not reported. These and common polymorphisms identified for this patient are available upon request.


Reclassification of Variants-Policy:

All detected alterations are evaluated according to American College of Medical Genetics and Genomics recommendations.(1) Variants are classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance. At this time, it is not standard practice for the laboratory to systematically review likely deleterious alterations or variants of uncertain significance that are detected and reported. 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.

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, et al: 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. Human 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