Test Catalog

Test Id : TPPTL

Tripeptidyl Peptidase 1 and Palmitoyl-Protein Thioesterase 1, Leukocytes

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

Evaluation of patients with clinical presentations suggestive of neuronal ceroid lipofuscinoses (NCL)

 

Aids in the differential diagnosis of infantile and late infantile NCL

 

This test is not useful for detecting carrier status of NCL.

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

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.

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

Fluorometric

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

TPP1 and PPT1, WBC

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

CLN1

CLN2

INCL

LINCL

NCL1

NCL2

Palmitoyl-Protein Thioesterase 1 (PPT1)

TPP1 (Tripeptidyl Peptidase 1)

NCL (Neuronal Ceroid Lipofuscinosis)

Batten disease

Specimen Type
Describes the specimen type validated for testing

Whole Blood ACD

Shipping Instructions

For optimal isolation of leukocytes, it is recommended the specimen arrive refrigerated within 6 days of collection to be stabilized. Collect specimen Monday through Thursday only and not the day before a holiday. Specimen should be collected and packaged as close to shipping time as possible.

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

Container/Tube:

Preferred: Yellow top (ACD solution B)

Acceptable: Yellow top (ACD solution A)

Specimen Volume: 6 mL

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

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

5 mL

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

Gross hemolysis 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 ACD Refrigerated (preferred) 6 days YELLOW TOP/ACD
Ambient 6 days YELLOW TOP/ACD

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

Evaluation of patients with clinical presentations suggestive of neuronal ceroid lipofuscinoses (NCL)

 

Aids in the differential diagnosis of infantile and late infantile NCL

 

This test is not useful for detecting carrier status of NCL.

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

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.

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. They are considered the most common of the neurogenetic storage disorders, with incidences ranging from 1.3 to 7 per 100,000 live births. Clinically, they are characterized by vision loss, seizures, mental regression, behavioral changes, movement disorders, and the accumulation of autofluorescent storage material in the brain and tissues. Although at least 12 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 and late-infantile NCL are caused primarily by defects in PPT1 and TPP1, respectively. Tissue damage is selective for the nervous system and many patients die in the first decade of life due to central nervous system degeneration.

 

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. Infantile NCL has an incidence of 1 in 20,000 in Finland and is rare elsewhere.

 

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, the molecular genetic test 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.

TRIPEPTIDYL PEPTIDASE 1

85-326 nmol/hour/mg protein

 

PALMITOYL-PROTEIN THIOESTERASE 1

20-93 nmol/hour/mg protein

Interpretation
Provides information to assist in interpretation of the test results

Tripeptidyl peptidase 1 (TPP1) enzyme activity or palmitoyl-protein thioesterase 1 (PPT1) enzyme activity below 5 nmol/hour/mg of protein is highly suggestive of late-infantile and infantile neuronal ceroid lipofuscinoses (NCL), respectively.

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

Some variants with an age of onset occurring in older individuals have been noted.

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

1. Mole S, Cotman S: Genetics of the neuronal ceroid lipofuscinoses (Batten disease). Biochem et Biophys Acta. 2015 Oct;1852:2237-2241

2. Kavianen R, Eriksson K, Losekoot M, et al: Juvenile-onset neuronal ceroid lipofuscinosis with infantile CLN1 mutation and palmitoyl-protein thioesterase deficiency. Eur J Neurol. 2007 Apr;14(4):369-372

3.Giugliani R, Vairo F, Beck M, et al: Lysosomal disorders. In: Sarafoglou K, Hoffman GF, Roth KS, eds. Pediatric Endocrinology and Inborn Errors of Metabolism. 2nd ed. McGraw-Hill Medical Division; 2017:983-1021

4. Nita DA, Mole SE, Minassian BA: Neuronal ceroid lipofuscinoses. Epileptic Disord. 2016 Sep 1;18(S2):73-88. doi: 10.1684/epd.2016.0844

5. Williams RE, Adams HR, Blohm M, et al: Management strategies for CLN2 disease. Pediatr Neurol. 2017 Apr;69:102-112. doi: 10.1016/j.pediatrneurol.2017.01.034

6. Mole SE, Anderson G, Band HA, et al: Clinical challenges and future therapeutic approaches for neuronal ceroid lipofuscinosis. Lancet Neurol. 2019 Jan;18(1):107-116. doi: 10.1016/S1474-4422(18)30368-5

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

The synthetic substrate for palmitoyl-protein thioesterase 1 (PPT1) is 4-methylumbelliferyl-6-thiopalmitoyl-beta-glucoside. The leukocytes are homogenized and combined with protein and a substrate and incubated. The reaction is stopped with a glycine buffer. The fluorescence of the 4-methylumbelliferone product is read using a fluorescence plate reader and activity is calculated based on amount of product formed during the 1-hour incubation period.(van Diggelen OP, Keulemans JL, Winchester B, et al: A rapid fluorogenic palmitoyl-protein thioesterase assay: pre and postnatal diagnosis of INCL. Mol Genet Metab. 1999 Apr;66(4):240-244; Cowan T, Pasquali M: Laboratory investigations of inborn errors of metabolism. In: Sarafoglou K, Hoffman GF, Roth KS, eds. Pediatric Endocrinology and Inborn Errors of Metabolism. 2nd ed. McGraw-Hill; 2017:1139-1158)

 

The synthetic substrate for tripeptidyl peptidase 1 (TPP1) is Ala-Ala-Phe-7-amido-4-methylcoumarin. The leukocytes are homogenized and combined with protein and a substrate and incubated. The reaction is stopped with a glycine buffer. The fluorescence of the 7-amino-4-methylcoumarin product is read using a fluorescence plate reader and activity is calculated based on amount of product formed during the 1-hour incubation period.(Sohar I, Lin L, Lobel P: Enzyme-based diagnosis of classical late infantile neuronal ceroid lipofuscinosis: comparison of tripeptidyl peptidase I and pepstatin-insensitive protease assays. Clin Chem. 2000 Jul;46(7):1005-1008; Cowan T, Pasquali M: Laboratory investigations of inborn errors of metabolism. In: Sarafoglou K, Hoffman GF, Roth KS, eds. Pediatric Endocrinology and Inborn Errors of Metabolism. 2nd ed. McGraw-Hill; 2017:1139-1158)

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.

Preanalytical processing: Monday through Saturday.

Assay performed: Twice per month

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

WBC homogenate: 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.

82657

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