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TPPTF
89540
TPPTL
89494
Test Performed By:
Medtox Laboratories, Inc.
402 W. County Road D
St. Paul, MN 55112
Tripeptidyl Peptidase 1 (TPP1) and Palmitoyl-Protein
Thioesterase 1 (PPT1), Fibroblasts
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 storage material with a characteristic appearance by electron microscopy. Currently, at
least 10 genetically distinct NCLs (CLN1-CLN10) are known. The age of onset and rate of deterioration
varies according to type of NCL. 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 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 CLN1 or CLN2 may allow for
identification of the disease causing mutations.
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
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, respectively.
Reference Values:
TPP1: 69-934 nmol/h/mg Prot
PPT1: 30-194 nmol/h/mg Prot
Clinical References: 1. Haltia M: The neuronal ceroid-lipofuscinoses: from past to present.
Biochem Biophys Acta 2006;1762:850-856 2. Kavianen R: Juvenile-onset neuronal ceroid liposuscinosis
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
Tripeptidyl Peptidase 1 (TPP1) and Palmitoyl-Protein
Thioesterase 1 (PPT1), Leukocytes
Clinical Information: The neuronal ceroid lipofuscinoses (NCL) comprise a group of recessively
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