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

Reporting Name

TPP1 and PPT1, Fibroblasts

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 when fibroblasts are available

 

NCL testing in fibroblast specimens

Additional Tests

Test ID Reporting Name Available Separately Always Performed
FIBR Fibroblast Culture Yes Yes
CRYOB Cryopreserve for Biochem Studies No Yes

Testing Algorithm

When this test is ordered, a fibroblast culture and cryopreservation for biochemical studies will always be performed at an additional charge. However, for multiple lysosomal enzyme assays on a patient utilizing fibroblast culture, only 1 culture is required regardless of the number of enzyme assays ordered. If viable cells are not obtained within 10 days, client will be notified.

Specimen Type

Tissue


Advisory Information


This test is not recommended for prenatal testing.



Specimen Required


Submit only 1 of the following specimens:

 

Specimen Type: Cultured fibroblasts

Container/Tube: T-75 or T-25 flask

Specimen Volume: 1 Full T-75 flask or 2 full T-25 flasks

Specimen Stability Information: Ambient (preferred)/Refrigerated <24 hours

 

Specimen Type: Skin biopsy

Container/Tube: Sterile container with any standard cell culture media (eg, minimal essential media, RPMI 1640). The solution should be supplemented with 1% penicillin and streptomycin. Tubes can be supplied upon request (Eagle's minimum essential medium with 1% penicillin and streptomycin: T115).

Specimen Volume: 4-mm punch

Specimen Stability Information: Refrigerated (preferred)/Ambient


Specimen Stability Information

Specimen Type Temperature Time
Tissue Varies

Reference Values

TRIPEPTIDYL PEPTIDASE 1

69-934 nmol/h/mg protein

 

PALMITOYL-PROTEIN THIOESTERASE 1

30-194 nmol/h/mg protein

Day(s) and Time(s) Performed

Friday

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-TPP1 and PPT1

88233-Fibroblast culture

88240-Cryopreservation for biochemical studies

LOINC Code Information

Test ID Test Order Name Order LOINC Value
TPPTF TPP1 and PPT1, Fibroblasts In Process

 

Result ID Test Result Name Result LOINC Value
50791 Specimen 31208-2
50792 Specimen ID 57723-9
50793 Source 31208-2
50794 Order Date 82785-7
50795 Reason For Referral 42349-1
50796 Method 49549-9
50797 TPP1, F 74576-0
50798 PPT1, F 34647-8
50799 Interpretation 59462-2
50800 Amendment In Process
50801 Reviewed By No LOINC Needed
50802 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 NCLs have traditionally been categorized based on age of symptom onset: 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/h/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

30-45 days depending on rapidity of growth

Method Name

TPPTF: Fluorometric Enzyme Assay
CRYOB: Fibroblast Subculture Followed by Cryopreservation and Storage

Forms

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.

Mayo Medical Laboratories | Genetics and Pharmacogenomics Catalog Additional Information:

mml-biochemical