Test Catalog

Test Id : PLSD

Lysosomal and Peroxisomal Storage Disorders Screen, Blood Spot

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

Evaluation of patients with a clinical presentation suggestive of a lysosomal storage disorder, specifically Gaucher, Niemann-Pick type A or type B, Pompe, Krabbe, Fabry disease, or mucopolysaccharidosis I; or a peroxisomal disorder, either X-linked adrenoleukodystrophy or Zellweger syndrome spectrum

Highlights

This is a screening test performed from a blood spot for a select number of lysosomal and peroxisomal disorders, including Gaucher disease, Fabry disease, Pompe disease, Krabbe disease, Niemann-Pick diseases A and B, mucopolysaccharidosis type I, Zellweger syndrome spectrum, and X-linked adrenoleukodystrophy.

 

Additional biochemical or molecular testing is required to confirm a diagnosis if enzyme deficiency is detected by this screening test.

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
MPSBS Mucopolysaccharidosis, BS Yes No
PSY Psychosine, BS Yes No
GPSY Glucopsychosine, BS Yes No
OXYBS Oxysterols, BS Yes No
LPCBS LysoPC by LC MS/MS, BS Yes No
PDBS Pompe Disease, BS Yes No
LGBBS Globotriaosylsphingosine, BS Yes No

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

Flow Injection Analysis-Tandem Mass Spectrometry (FIA-MS/MS)

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

Lysosomal/Peroxisomal D/O Scrn, BS

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

Acid Alpha-Glucosidase

Acid Beta-Glucosidase

Acid Maltase Deficiency

Alpha Galactosidase A

Anderson-Fabry Disease

Beta-Glucosidase

Ceramide Trihexosidase

Cerebrosidase B-Galactosidase

Cerebrosidase Beta-Galactosidase

Fabry Disease

GAA

Galactocerebrosidase

Galactosylceramidase

GALC

Gaucher Disease

GBA

GLA

Globoid Cell Leukodystrophy

Glucocerebrosidase Deficiency

Glycogen Storage Disease Type II (GSD II)

GSD II (Glycogen Storage Disease Type II)

Krabbe Disease

LDSBS

LSD Screen

LSDBS

Lysosomal Storage Disorder Screen

Niemann-Pick Disease (NPD)

NPD (Niemann-Pick Disease)

Pompe Disease

Sphingomyelinase Deficiency

Mucopolysaccharidosis type I

Alpha-L-iduronidase

MPS IH (Hurler syndrome)

MPS IS (Sheie syndrome)

MPS IH/S (Hurler-Scheie syndrome)

Adrenoleukodystrophy (ALD)

X-linked adrenoleukodystrophy (XALD)

Adrenomyeloneuropathy

Zellweger Syndrome

Zellweger Spectrum Syndrome (ZSS)

Peroxisomal biogenesis disorders

Specimen Type
Describes the specimen type validated for testing

Whole blood

Ordering Guidance

To evaluate adult patients with a clinical presentation suggestive of adrenomyeloneuropathy, the recommended test is POX / Fatty Acid Profile, Peroxisomal (C22-C26), Serum. Lysophosphatidylcholine concentrations may not be consistently elevated in adult blood spots.

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

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

Container/Tube:

Preferred: Card-Blood Spot Collection (Filter Paper)

Acceptable: PerkinElmer 226 (formerly Ahlstrom 226) filter paper, Munktell filter paper, Whatman Protein Saver 903 paper, or blood collected in tubes containing ACD, EDTA, or heparin and dried on acceptable filter paper

Specimen Volume: 2 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 via fingerstick: https://vimeo.com/508490782 .

2. Completely fill at least 2 circles on the filter paper card (approximately 100 microliters blood per circle).

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

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

5. Do not stack wet specimens.

6. Keep specimen dry.

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.

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. Biochemical Genetics Patient Information (T602) in Special Instructions

3. If not ordering electronically, complete, print, and send a Biochemical Genetics Test Request (T798) with the specimen.

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

1 Blood spot

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

Shows serum rings
Insufficient specimen
Layering
Multiple applications
Incubated/exposed to temperatures above 37 degrees C
Reject
 

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
Whole blood Refrigerated (preferred) 56 days FILTER PAPER
Frozen 56 days FILTER PAPER
Ambient 7 days FILTER PAPER

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

Evaluation of patients with a clinical presentation suggestive of a lysosomal storage disorder, specifically Gaucher, Niemann-Pick type A or type B, Pompe, Krabbe, Fabry disease, or mucopolysaccharidosis I; or a peroxisomal disorder, either X-linked adrenoleukodystrophy or Zellweger syndrome spectrum

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

Lysosomes are intracellular organelles that contain hydrolytic enzymes to degrade a variety of macromolecules. Lysosomal storage disorders are a diverse group of inherited diseases where macromolecules accumulate due to defects in their transport mechanisms across the lysosomal membrane or due to defective lysosomal enzyme function. Accumulation of these macromolecules in the lysosomes leads to cell damage and, eventually, organ dysfunction. More than 50 lysosomal storage disorders have been described with a wide phenotypic spectrum.

 

Gaucher disease results from a deficiency of the enzyme, beta-glucosidase caused by variants in the GBA gene. Beta-glucosidase facilitates the lysosomal degradation of glucosylceramide (glucocerebroside) and glucopsychosine (glucosylsphingosine). There are 3 described types of Gaucher disease with varying clinical presentations and age of onset, from a perinatal lethal disorder to an asymptomatic type. Features of all types of Gaucher disease include hepatosplenomegaly and hematological abnormalities. Treatment is available in the form of enzyme replacement therapy, substrate reduction therapy, and chaperone therapy for types 1 and 3. Currently, only supportive therapy is available for type 2.

 

Niemann-Pick disease types A and B are caused by a deficiency of sphingomyelinase due to variants in the SMPD1 gene. This results in extensive storage of sphingomyelin and cholesterol in the liver, spleen, lungs, and, to a lesser degree, brain. Classification of type A versus type B is based on the age of onset as well as the severity of symptoms. Niemann-Pick type A disease is more severe than type B and characterized by early onset with feeding problems, dystrophy, persistent jaundice, development of hepatosplenomegaly, neurological deterioration, deafness, and blindness leading to death by 3 years of age. Niemann-Pick type B disease is limited to visceral symptoms with survival into adulthood. Some patients have been described with intermediary phenotypes. Characteristic of the disease are large lipid-laden foam cells. Approximately 50% of cases have cherry-red spots in the macula.  Treatment is supportive, although there are clinical trials in place.

 

Pompe disease, also known as glycogen storage disease type II, is an autosomal recessive disorder caused by a deficiency of the lysosomal enzyme acid alpha-glucosidase (GAA; acid maltase) due to variants in the GAA gene. The estimated incidence is 1 in 40,000 live births. In Pompe disease, glycogen that is taken up by lysosomes during physiologic cell turnover accumulates, causing lysosomal swelling, cell damage, and, eventually, organ dysfunction. The clinical presentation of Pompe disease ranges from a rapidly progressive infantile variant, which is uniformly lethal if untreated, to a more slowly progressive late-onset variant. All disease variants are eventually associated with progressive muscle weakness and respiratory insufficiency. Cardiomyopathy is associated almost exclusively with the infantile form. Enzyme replacement therapy is available for all variants and should be started as soon as possible for patients with the infantile variant and at the first signs of muscle weakness in the later onset variants.

 

Krabbe disease (globoid cell leukodystrophy) is an autosomal recessive disorder caused by variants in the GALC gene resulting in a deficiency of galactocerebrosidase (GALC, galactosylceramide beta-galactosidase). Galactosylceramide (as with sulfated galactosylceramide) is a lipid component of myelin. The absence of GALC results in globular, distended, multinucleated bodies in the basal ganglia, pontine nuclei, and cerebral white matter. There is severe demyelination throughout the brain with progressive cerebral degenerative disease affecting primarily the white matter. Severely affected individuals typically present between 3 to 6 months of age with increasing irritability and sensitivity to stimuli. Rapid neurodegeneration, including white matter disease, follows with death usually occurring by 2 years of age. A subset of individuals has later onset forms of the disease, which are characterized by ataxia, vision loss, weakness, and psychomotor regression. They can present anywhere from age 6 months to the seventh decade of life and, based on newborn screening experience in New York, appear to be more common than the earlier onset variants. Psychosine has been shown to be elevated in patients with clinical signs and symptoms of disease and, therefore, may be a useful biomarker for the presence of disease or disease progression. The only available therapy is hematopoietic stem cell transplantation that is best performed prior to the onset of clinical symptoms.

 

Fabry disease, caused by variants in the GLA gene, is an X-linked recessive disorder with an incidence of approximately 1 in 50,000 males. Symptoms result from a deficiency of the enzyme alpha-galactosidase A (GLA; ceramide trihexosidase). Reduced GLA activity results in accumulation of glycosphingolipids in the lysosomes of both peripheral and visceral tissues. Severity and onset of symptoms are dependent on the residual GLA activity. Males with less than 1% GLA activity have the classic form of Fabry disease. Symptoms can appear in childhood or adolescence and usually include acroparesthesias (pain crises), multiple angiokeratomas, reduced or absent sweating, and corneal opacity. Renal insufficiency, leading to end-stage kidney disease and cardiac and cerebrovascular disease, generally occurs in middle age. Males with greater than1% GLA activity may present with a variant form of Fabry disease with onset of symptoms later in life. The renal variant generally has onset of symptoms in the third decade. The most prominent feature in this form is renal insufficiency and, ultimately, end stage kidney disease. Individuals with the renal variant may or may not share other symptoms with the classic form of Fabry disease. Individuals with the cardiac variant are often asymptomatic until they present with cardiac findings such as cardiomyopathy or mitral insufficiency in the fourth decade. The cardiac variant is not associated with kidney failure. Female patients who are carriers of Fabry disease can have clinical presentations ranging from asymptomatic to severely affected. Enzyme replacement therapy is a treatment option for both male and female patients with Fabry disease.

 

Mucopolysaccharidosis I (MPS I) is an autosomal recessive disorder caused by a reduced or absent activity of the alpha-L-iduronidase (IDUA) enzyme. Reduced IDUA activity results in accumulation of glycosaminoglycans (mucopolysaccharides) within the lysosome. The clinical presentation and severity of symptoms of MPS I are variable, ranging from severe disease to attenuated variants (historically known as Hurler-Scheie disease and Scheie disease) that generally present with a later onset and a milder clinical presentation. In general, symptoms may include coarse facies, progressive dysostosis multiplex, hepatosplenomegaly, corneal clouding, hearing loss, mental retardation or learning difficulties, and cardiac valvular disease. MPS-I is caused by genetic variants in the IDUA gene and has an estimated incidence of approximately 1 in 100,000 live births. Treatment options include hematopoietic stem cell transplantation and enzyme replacement therapy.

 

Peroxisomes are organelles present in all human cells except mature erythrocytes. They carry out essential metabolic functions including beta-oxidation of very long-chain fatty acids, alpha-oxidation of phytanic acid, and biosynthesis of plasmalogen and bile acids. Peroxisomal disorders include 2 major subgroups: disorders of peroxisomal biogenesis and single peroxisomal enzyme/transporter defects. Peroxisome biogenesis defects such as Zellweger spectrum disorders are characterized by defective assembly of the entire organelle, whereas in single enzyme/transporter defects such as X-linked adrenoleukodystrophy (XALD), the organelle is intact, but a specific function is disrupted. These disorders are clinically diverse and range in severity from neonatal lethal to milder, later onset variants.

 

XALD is a disorder affecting the nervous system, adrenal cortex, and testis. It is the most common of the peroxisomal disorders, affecting 1 in 17,000 to 1 in 21,000 male patients. A defect in the ABCD1 gene is responsible for the disease. XALD shows a wide range of phenotypic expressions. The clinical phenotypes occurring in male patients can be subdivided in 4 main categories: cerebral inflammatory, adrenomyeloneuropathy (AMN), Addison only, and asymptomatic. The first 2 phenotypes account for almost 80% of the patients, while the frequency of the asymptomatic category diminishes with age and is very rare after age 40. It is estimated that approximately 50% of heterozygous individuals are symptomatic and develop an AMN-like syndrome. Treatment options are hormone replacement therapy, dietary intervention, or hematopoietic stem cell transplantation.

 

Zellweger syndrome spectrum (ZSS) is a continuum of severe disorders affecting the nervous system, vision, hearing, and liver function. Most individuals present in infancy, but adult patients have been identified. The prevalence of ZSS is 1 in 50,000. ZSS follows autosomal recessive inheritance. At least 12 different genes have been implicated in ZSS, with approximately 60% to 70% of variants occurring in PEX1. The clinical phenotypes include Zellweger syndrome, neonatal adrenoleukodystrophy (NALD), and infantile Refsum disease (IRD). Individuals with Zellweger syndrome typically die within the first year of life without making any developmental progress. Individuals with NALD or IRD typically present in childhood with developmental delays, vision loss, and hearing loss, and have a much slower disease progression. There is no specific treatment for ZSS.

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.

Disease

Marker

Normal range

Gaucher

Acid beta-glucosidase

> or =1.75 nmol/mL/hr

Niemann-Pick A/B

Sphingomyelinase

> or =2.5 nmol/mL/hr

Pompe

Acid alpha-glucosidase

> or =3.0 nmol/mL/hr

Krabbe

Galactocerebrosidase

> or =0.4 nmol/mL/hr

Fabry

Alpha-galactosidase

> or =2.75 nmol/mL/hr

MPS I

Alpha-L-iduronidase

> or =2.0 nmol/mL/hr

NA

C20 Lysophosphatidylcholine

< or =1.00 mcg/mL

NA

C22 Lysophosphatidylcholine

< or =0.25 mcg/mL

ALD/PBD/ALDH

C24 Lysophosphatidylcholine

< or =0.30 mcg/mL

ALD/PBD/ALDH

C26 Lysophosphatidylcholine

< or =0.30 mcg/mL

 

Interpretation
Provides information to assist in interpretation of the test results

An interpretive report will be provided.

 

When abnormal results are detected, a detailed interpretation is given, including an overview of the results and of their significance, a correlation to available clinical information, elements of differential diagnosis, recommendations for additional biochemical testing, and in vitro confirmatory studies (enzyme assay, molecular analysis), and a phone number to reach one of the laboratory directors in case the referring physician has additional questions.

 

Abnormal results are not sufficient to conclusively establish a diagnosis of a particular disease. To verify a preliminary diagnosis based on the analysis, independent biochemical (eg, in vitro enzyme assay) or molecular genetic analyses are required.

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

A positive test result is strongly suggestive of a diagnosis but needs follow-up by stand-alone biochemical or molecular assay.

 

Carrier status (heterozygosity) for these conditions cannot be reliably detected.

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

1. Reuser AJ, Verheijen FW, Bali D, et al: The use of dried blood spot samples in the diagnosis of lysosomal storage disorders--current status and perspectives. Mol Genet Metab. 2011 Sep-Oct;104(1-2):144-148. doi: 10.1016/j.ymgme.2011.07.014

2. Klouwer FCC, Ferdinandusse S, van Lenthe H, et al: Evaluation of C26:0-lysophosphatidylcholine and C26:0-carnitine as diagnostic markers for Zellweger spectrum disorders. J Inherit Metab Dis. 2017 Nov;40(6):875-881. doi: 10.1007/s10545-017-0064-0

3. Huffnagel IC, van de Beek MC, Showers AL, et al: Comparison of C26:0-carnitine and C26:0-lysophosphatidylcholine as diagnostic markers in dried blood spots from newborns and patients with adrenoleukodystrophy. Mol Genet Metab. 2017 Dec;122(4):209-215

4. Part 15 Peroxisomes. In: Valle DL, Antonarakis S, Ballabio A, Beaudet AL, Mitchell GA. eds. The Online Metabolic and Molecular Bases of Inherited Disease. McGraw-Hill; 2019. Accessed June 16, 2021. Available at https://ommbid.mhmedical.com/book.aspx?bookid=2709#225069419

5 Part 16 Lysosomal disorders. In: Valle DL, Antonarakis S, Ballabio A, Beaudet AL, Mitchell GA. eds. The Online Metabolic and Molecular Bases of Inherited Disease. McGraw-Hill; 2019. Accessed June 16, 2021. Available at https://ommbid.mhmedical.com/book.aspx?bookid=2709#225069419

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

Two 1/8-inch dried blood spots (DBS) are excised from a single specimen. The enzymes are extracted by incubating the specimens with a mix of substrate and internal standard for acid sphingomyelinase, beta-glucocerebrosidase, alpha-glucosidase, alpha-galactosidase, galactocerebrosidase, and alpha-L-iduronidase. The sample is then purified by liquid-liquid extraction. The second DBS is extracted with methanol containing d4-C26 lysophosphatidylcholine. The resulting extracts are then combined, evaporated and reconstituted before analysis by tandem mass spectrometry.(Unpublished Mayo method)

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

No

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.

Monday through Sunday

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.

2 to 8 days

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

6 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.

83789

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 | 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