Children with CLN2 disease

Laboratory testing

Enzymatic and/or molecular testing is necessary to make a definitive diagnosis of CLN2 disease

Lab testing for CLN2 disease is straightforward

Experts define the gold standard for laboratory diagnosis of CLN2 disease as demonstration of deficient tripeptidylpeptidase 1 (TPP1) enzyme activity followed by identification of two pathogenic mutations in the CLN2/TPP1 gene.1

If it is not possible to perform both TPP1 enzyme assay and molecular testing due to local restrictions:1

  • Deficient TPP1 enzyme activity in leukocytes or fibroblasts is diagnostic when consistent with clinical signs of CLN2 disease
  • Detection of two pathogenic mutations, one for each allele in the CLN2/TPP1 gene, is diagnostic when consistent with clinical signs of CLN2 disease

There are two commonly reported mutations associated with CLN2 disease (c.509-1G>C and c.622C>T), and at least one of these two mutations can be present in up to 89% of patients with CLN2 disease.1,2

Enzymatic testing to assess TPP1 activity1

Enzymatic testing to assess TPP1 activity
  • Following the laboratory’s TPP1 enzyme activity, test sample collection and shipment guidelines are important, as incorrect sample collection procedures or storing conditions can affect results1

Molecular testing of CLN2/TPP1 gene

Expert consensus recommends that once TPP1 deficiency is confirmed, molecular testing should be performed to identify mutations in the CLN2/TPP1 gene.1

Molecular testing of CLN2/TPP1 gene1

Molecular testing of CLN2/TPP1 gene
  • Molecular testing alone can be diagnostic if two known pathogenic mutations are detected, one in each allele1
    • In the absence of clinical signs or family history, or when detected alterations are not readily interpretable, enzymatic testing may be used to corroborate molecular findings
  • Molecular testing is useful for genetic counselling and family planning1
Enzymatic and/or molecular testing are definitive ways to diagnose CLN2 disease.

References: 1. Fietz M et al. Diagnosis of neuronal ceroid lipofuscinosis type 2 (CLN2 disease): Expert recommendations for early detection and laboratory diagnosis. Mol Genet Metab. 2016; 119:160-167. 2. Kousi M et al. Update of the mutation spectrum and clinical correlations of over 360 mutations in eight genes that underlie the neuronal ceroid lipofuscinoses. Hum Mutat. 2012;33:42-63. 3. Barcenas M et al. Anal Chem 2014;86:7962–7968.