CLN2 disease

CLN2 disease is a rapidly progressing, treatable paediatric neurodegenerative disorder presenting with seizures and language delay as early hallmark signs and symptoms.1

CLN2 disease:

  • Is an autosomal recessive lysosomal storage disorder (LSD)2
  • Is one of the most common forms of neuronal ceroid lipofuscinosis (NCL)2
  • Has an estimated incidence of ~0.5 per 100,000 live births3
  • Most commonly presents as the late–infantile phenotype4
  • Mutations in the CLN2/TPP1 gene, which is located on chromosome 11p15 [63], result in deficient lysosomal activity of tripeptidylpeptidase 1 (TPP1)2,5
  • Results in a complete loss of cognitive abilities, motor function and vision by approximately 6 years of age2

CLN2 disease presents both classically and atypically4

CLN2 disease, classic phenotype:4

  • Late–infantile onset
    • The majority of diagnosed cases present with this phenotype and progress in a rapid and predictable manner

CLN2 disease, atypical phenotype:4-8

  • Age of onset, rate of progression and symptom progression vary, for example:
    • Infantile, with onset within the first year of life
    • Late–infantile onset with a protracted progression and patients may live into their 20s
    • Juvenile onset with a classic progression
  • Residual TPP1 enzyme activity is more common in atypical CLN2 phenotypes

CLN2 disease experts have identified a new path to expedite earlier diagnosis in children with CLN2 disease based on probing around early language development9

CLN2 disease should be suspected in children aged 2–4 with new-onset, unprovoked seizures preceded by early language delay

  • In CLN2 disease, onset of unprovoked seizures typically occurs between ages 2 and 4; febrile seizures may also occur1,10
  • 83% of children with CLN2 disease experience delay of early language development11
  • In a minority of cases, other developmental delays or ataxia may be the first sign, though these can often occur along with the language delay6
Probing on early language development in children who have had seizures can enable earlier diagnosis of CLN2 disease and access to specific care.

References: 1. Schulz A et al. NCL diseases–clinical perspectives. Biochimica et Biophysica Acta. 2013;1832:1801-1806. 2. Mole SE and Williams RE. Neuronal ceroid-lipofuscinoses. 2001 Oct 10 [Updated 2013 Aug 1]. In: Pagon RA, Adam MP, Ardinger HH, et al., eds. GeneReviews® [internet]. Seattle, WA: University of Washington; 1993-2016. 3. Claussen M et al. Incidence of neuronal ceroid-lipofuscinoses in West Germany: variation of a method for studying autosomal recessive disorders. Am J Med Genet. 1992;42:536-538. 4. Mole SE et al. Correlations between genotype, ultrastructural morphology and clinical phenotype in the neuronal ceroid lipofuscinoses. Neurogenetics. 2005;6:107-126. 5. 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. 6. Chang M et al. CLN2. In: Mole S, Williams R, and Goebel H, eds. The neuronal ceroid lipofuscinoses (Batten Disease). 2nd ed. Oxford, United Kingdom: Oxford University Press; 2011:80-109. 7. Williams RE et al. Diagnosis of the neuronal ceroid lipofuscinoses: an update. Biochimica et Biophysica Acta. 2006;1762:865-872. 8. Steinfeld R et al. Late infantile neuronal ceroid lipofuscinosis: quantitative description of the clinical course in patients with CLN2 mutations. Am J Med Genet. 2002;112:347-354. 9. 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. 10. 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. 11. Nickel M et al. Disease characteristics and progression in patients with late-infantile neuronal ceroid lipofuscinosis type 2 (CLN2) disease: an observational cohort study. Lancet Child Adolesc Health 2018;2(8):582–590.