Test Catalog

Test Id : NCLBS

Neuronal Ceroid Lipofuscinosis, Two-Enzyme Panel, Blood Spot

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

Supporting the biochemical diagnosis of two neuronal ceroid lipofuscinoses, CLN1 and CLN2


This test is not useful for carrier detection.

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

This test provides diagnostic testing for individuals with clinical signs and symptoms suspicious for neuronal ceroid lipofuscinosis 1 or 2 (CLN1 or CLN2). If an enzyme deficiency is detected by this screening test, additional biochemical or molecular testing is required to confirm a diagnosis.

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

Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS)

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


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

CLN1 and CLN2, BS

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




Palmitoyl-protein thioesterase 1


Tripeptidyl peptidase 1


Specimen Type
Describes the specimen type validated for testing

Whole blood

Ordering Guidance

This blood test is an appropriate first step for individuals between 0 and 4 years of age who present with symptoms consistent with neuronal ceroid lipofuscinosis.

Necessary Information

1. Patient's age is required.

2. Reason for testing is required


Question ID Description Answers
BG757 Reason for Referral Rule out CLN1
Rule out CLN2
Follow up of known CLN1
Follow up of known CLN2
Not Provided

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

Submit only 1 of the following specimen types:



Specimen Type: Blood spot

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


Preferred: Blood Spot Collection Card

Acceptable: Whatman Protein Saver 903 Paper, PerkinElmer 226 filter paper, Munktell filter paper, or blood collected in tubes containing ACD or EDTA and dried on filter paper.

Specimen Volume: 2 Blood spots

Collection Instructions:

1. An alternative blood collection option for a patient 1 year of age or older is a fingerstick. See How to Collect Dried Blood Spot Samples via fingerstick.

2. At least 2 spots should be complete, ie, unpunched.

3. Let blood dry on filter paper at room 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.

Specimen Stability Information: Refrigerated (preferred) 60 days/Ambient 7 days/Frozen 60 days

Additional Information:

1. For collection instructions, see Blood Spot Collection Instructions

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

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



Specimen Type: Whole Blood


Preferred: Lavender top (EDTA)

Acceptable: Yellow top (ACD)

Specimen Volume: 2 mL

Collection Instructions: Send whole blood specimen in original tube. Do not aliquot.

Specimen Stability Information: Refrigerate (preferred) 7 days/Ambient 48 hours

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


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:

-Informed Consent for Genetic Testing (T576)

-Informed Consent for Genetic Testing-Spanish (T826)

2. Biochemical Genetics Patient Information (T602)

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

Blood Spots: 1

Whole Blood: 0.5 mL

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

Blood spot specimen that shows serum rings or has multiple layers Reject
Insufficient specimen Reject
Unapproved filter papers 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 Varies

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

Supporting the biochemical diagnosis of two neuronal ceroid lipofuscinoses, CLN1 and CLN2


This test is not useful for carrier detection.

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

This test provides diagnostic testing for individuals with clinical signs and symptoms suspicious for neuronal ceroid lipofuscinosis 1 or 2 (CLN1 or CLN2). If an enzyme deficiency is detected by this screening test, additional biochemical or molecular testing is required to confirm a diagnosis.

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

The neuronal ceroid lipofuscinoses (NCL) comprise a group of recessively inherited neurodegenerative disorders involved in lysosomal protein catabolism. Clinically they are characterized by vision loss, seizures, developmental regression, behavioral changes, movement disorders, and distinguished from other neurodegenerative disorders by the accumulation of auto fluorescent storage material in the brain and tissues. Although at least 13 different genes have been identified, the NCL have traditionally been categorized based on the age of onset of symptoms: infantile, late-infantile, juvenile, and adult. Infantile (CLN1) and late-infantile NCL (CLN2) are caused by defects in palmitoyl-protein thioesterase 1 (PPT1) and tripeptidyl peptidase 1 (TPP1), respectively. Deficiency of tripeptidyl peptidase is also a cause of autosomal recessive spinocerebellar ataxia-7.


Children affected by infantile NCL (CLN1) typically have normal growth and development until about 6 to 12 months of age. Slowed head growth occurs at around 9 months followed by psychomotor degeneration, seizures, and progressive macular degeneration leading to blindness by the age 2 years. CLN1 is caused by a deficiency of the lysosomal enzyme palmitoyl-protein thioesterase 1 (PPT1), which cleaves long-chain fatty acids (usually palmitate) from cysteine residues. Electron microscopy shows granular osmophilic deposits in most cell types. PPT1 is thought to play an active role in various cell processes including apoptosis, endocytosis, and lipid metabolism.


The late infantile form of NCL (CLN2) is primarily caused by deficiency of the lysosomal enzyme tripeptidyl peptidase 1 (TPP1), which cleaves tripeptides from the N-terminus of polypeptides. Tissue damage results from the defective degradation and consequent accumulation of storage material with a curvilinear profile by electron microscopy. There is widespread loss of neuronal tissue especially in the cerebellum and hippocampal region. Disease onset occurs at 2 to 4 years of age with seizures, ataxia, myoclonus, psychomotor retardation, vision loss, and speech impairment.


Diagnostic strategy depends on the age of onset of symptoms. In children presenting between the ages 0 to 4 years, enzyme assay of PPT1 and TPP1 is an appropriate first step. For other patients suspected of having an NCL, molecular genetic testing of CLN genes is available; see NCLGP / Neuronal Ceroid Lipofuscinosis (Batten Disease) Gene Panel, Varies.

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.

Palmitoyl-protein thioesterase 1: >10.0 nmol/mL/h

Tripeptidyl peptidase 1: >27.0 nmol/mL/h


An interpretative report will be provided.

Provides information to assist in interpretation of the test results

Abnormal results are not sufficient to establish a diagnosis of a particular disease. To verify a preliminary diagnosis based on this assay, additional biochemical or molecular genetic analyses are required.


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 genetic analysis), and a phone number to reach one of the laboratory directors in case the referring physician has additional questions.

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

Deficiency of tripeptidyl peptidase 1 (TPP1) can also be indicative of autosomal recessive spinocerebellar ataxia-7.


Individuals with pseudodeficiency alleles can show reduced enzyme activity.


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


Enzyme levels may be normal in individuals receiving enzyme replacement therapy or who have undergone hematopoietic stem cell transplant.

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

1. Hofmann SL, Peltonen L. The neuronal ceroid lipofuscinoses. In: Valle DL, Antonarakis S, Ballabio A, Beaudet AL, Mitchell GA. eds. The Online Metabolic and Molecular Bases of Inherited Disease. McGraw-Hill; Accessed July 18, 2023. Available at https://ommbid.mhmedical.com/content.aspx?bookid=2709&sectionid=225548100

2. Kohlschutter A, Schulz A, Bartsch U, Storch S. Current and emerging treatment strategies for neuronal ceroid lipofuscinoses. CNS Drugs. 2019;33(4):315-325. doi:10.1007/s40263-019-00620-8

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

One dried blood spot sample (DBS) is incubated with a mix of substrate and internal standard (IS) for iduronate 2-sulfatase, heparan N-sulfatase, alpha-N-acetylglucosaminidase, N-acetylgalactosamine-sulfate, beta-galactosidase, arylsulfatase B, beta-glucuronidase, and tripeptidyl peptidase 1. A second DBS sample is incubated with a mix of substrate and IS for acetyl-CoA:alpha-glucosaminide N-acetyltransferase; and a third DBS sample with a mix of substrate and IS for palmitoyl-protein thioesterase 1. Following overnight incubation, the samples are combined, extracted by liquid-liquid extraction, and analyzed by tandem mass spectrometry. (Unpublished Mayo method)

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


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.


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.

8 to 15 days

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

1 year

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


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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. It 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.


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
NCLBS CLN1 and CLN2, BS 101348-1
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.
BG757 Reason for Referral 42349-1
618435 Palmitoyl-protein thioesterase 1 59246-9
618436 Tripeptidyl peptidase 1 72498-9
618437 Interpretation 59462-2
618434 Reviewed 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 | PHP Pdf | CMS 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