Children with CLN2 Disease

Early signs

Emerging clinical findings indicate that CLN2 disease should be suspected in all children aged 2—4 with new-onset, unprovoked seizures preceded by a history of language delay

  • In CLN2 disease, onset of unprovoked seizures typically occurs between ages 2—4; febrile seizures may also occur1,2
  • In some cases, ataxia or other developmental delays may also occur or may be the first signs of CLN2 disease3

When a young child presents with seizures, ask parents detailed questions about early language development to raise the index of suspicion for CLN2 disease

  • Language delay and seizures may be common symptoms on their own, but the combination of early language delay prior to seizure presentation should raise the index of suspicion for CLN2 disease4,5
  • Test for CLN2 disease in children aged 2—4 with these two hallmark symptoms

CLN2 disease diagnostic algorithm5

CLN2 disease diagnostic algorithm

Adapted from Fietz et al. 2016.

* Additional clinical assessments may be warranted, such as brain MRI, OCT/VEP/ERG/FA, and EM biopsy.

TPP1 enzyme activity may be measured in sample types such as dried blood spots or saliva. PPT1 enzyme activity (CLN1 disease) is useful to assess with TPP1.

‡ TPP1 enzyme activity testing in other sample types can also be diagnostic.

§ Includes single gene sequencing, gene panels, or whole exome/genome sequencing.

References: 1. Schulz A et al. NCL diseases – clinical perspectives. Biochimica et Biophysica Acta. 2013;1832:1801-1806. 2. Pérez-Poyato MS et al. Late infantile neuronal ceroid lipofuscinosis: mutations in the CLN2 gene and clinical course in Spanish patients. J Child Neurol. 2013;28:470-478. 3. Worgall S et al. Treatment of late infantile neuronal ceroid lipofuscinosis by CNS administration of a serotype 2 adeno-associated virus expressing CLN2 cDNA. Hum Gene Ther. 2008;19:463-474. 4. Nickel M et al. Natural history of CLN2 disease: quantitative assessment of disease characteristics and rate of progression. Poster session presented at: The 12th Annual WORLD Symposium; February – March 2016; San Diego, CA. 5. 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