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Test ID: TPPTL Tripeptidyl Peptidase 1 (TPP1) and Palmitoyl-Protein Thioesterase 1 (PPT1), Leukocytes

Reporting Name

TPP1 and PPT1, WBC

Useful For

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

 

An aid in the differential diagnosis of infantile and late infantile NCL

Specimen Type

Whole Blood ACD


Shipping Instructions


For optimal isolation of leukocytes, it is recommended the specimen arrive refrigerate within 144 hours of draw to be stabilized. Draw specimen Monday through Thursday only and not the day before a holiday. Specimen should be drawn and packaged as close to shipping time as possible.



Specimen Required


Container/Tube:

Preferred: Yellow top (ACD solution B)

Acceptable: Yellow top (ACD solution A)

Specimen Volume: 6 mL

Collection Instructions: Do not transfer blood to other containers.


Specimen Minimum Volume

5 mL

Specimen Stability Information

Specimen Type Temperature Time
Whole Blood ACD Refrigerated (preferred) 6 days
  Ambient  72 hours

Reference Values

TRIPEPTIDYL PEPTIDASE 1

85-326 nmol/hour/mg protein

 

PALMITOYL-PROTEIN THIOESTERASE 1

20-93 nmol/hour/mg protein

Day(s) and Time(s) Performed

Specimens are processed Monday through Sunday.

Assay is performed Friday; 8 a.m.

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 U.S. Food and Drug Administration.

CPT Code Information

82657

LOINC Code Information

Test ID Test Order Name Order LOINC Value
TPPTL TPP1 and PPT1, WBC In Process

 

Result ID Test Result Name Result LOINC Value
50688 Specimen 31208-2
50689 Specimen ID 57723-9
50690 Source 31208-2
50691 Order Date 82785-7
50692 Reason for Referral 42349-1
50693 Method 49549-9
50694 TPP1L In Process
50695 PPT1L In Process
50696 Interpretation 59462-2
50697 Amendment In Process
50698 Reviewed By No LOINC Needed
50699 Release Date 82772-5

Clinical Information

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, 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. There is an overall incidence in the United States estimated at 1 in 12,500.

 

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 of 2. 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 (GRODs) 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. In addition, molecular genetic testing of PPT1 or TPP1 may allow for identification of the disease causing mutations.

Interpretation

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

Clinical Reference

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

2. Kavianen R: Juvenile-onset neuronal ceroid lipofuscinosis with infantile CLN1 mutation and palmitoyl-protein thioesterase deficiency. Eur J Neur 2007;14:369-372

3. Enns GM, Steiner RD, Cowan TM: Lysosomal disorders. In Pediatric Endocrinology and Inborn Errors of Metabolism. Edited by K Sarafoglou, GF Hoffmann, KS Roth, New York, McGraw-Hill Medical Division, 2009, pp 749-750

4. Mole SE, Williams RE: Neuronal Ceroid-Lipofuscinoses. In GeneReviews. Edited by RA Pagon, MP Adam, HH Ardinger, et al: University of Washington, Seattle, 1993-2016. Updated 2013 Aug 1. Available at www.ncbi.nlm.nih.gov/books/NBK1428/

Analytic Time

8 days

Method Name

Fluorometric

Forms

1. New York Clients-Informed consent is required. Please document on the request form or electronic order that a copy is on file. An Informed Consent for Genetic Testing (T576) is available in Special Instructions.

2. Biochemical Genetics Patient Information (T602) in Special Instructions

Mayo Medical Laboratories | Genetics and Pharmacogenomics Catalog Additional Information:

mml-biochemical