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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.

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