Children with CLN2 disease

Signs & symptoms

Recognising the early signs

Seizures are the symptom that most often prompts parents to seek medical attention

  • Unprovoked seizures commonly present in the majority of children with CLN2 disease between the ages of 2 and 41
    • For some children, the first seizure can be febrile in nature or onset may occur later2,3
  • Multiple types of seizures can be observed, including generalised tonic-clonic, absence, myoclonic, atonic, clonic and tonic3,5,6
  • Seizures continue over the course of the disease and become intractable, often requiring multiple anti-epileptic drugs4
  • Myoclonus - both epileptic and non-­epileptic - is the most predominant feature5

Children are often diagnosed with epilepsy without a further workup for CLN2 disease.4,7
Misdiagnosis can result in:

  • Treatment with anti-­epileptic drugs, with side effects that can mask and delay the recognition of CLN2 disease4
  • Tests delayed until the disease has significantly progressed5,7

Early language delay has been identified as a sign of CLN2 disease in the majority of patients8

83% of children with CLN2 disease experienced delay of early language development8

  • Criteria for identifying early language delay:8
    • First single words acquired at 18 months (or later/never)
    • First two-word sentences at 24 months (or later/never)
    • First full sentences at 36 months (or later/never)

Percentage of ‘late talkers’ in children with CLN2 disease and in age-matched controls8

Early-language-delay studies in children with CLN2 versus controls
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 level of suspicion for CLN2 disease. It is important to ask carers about early language development, even if current abilities appear normal.7,8

Not all children will have early language delay - some children may exhibit ataxia or other developmental delays as early symptoms.9

When children aged 2—4 present with new-onset, unprovoked seizures…

  • PROBE on early language development, even if current abilities appear normal
  • FOCUS on key points of age-specific language acquisition before the onset of overt symptoms
  • TEST for CLN2 disease in children who have these two hallmark symptoms
Based on emerging data, probing on early language development preceding the onset of seizures can enable earlier diagnosis of CLN2 disease.
Dr Angela Schulz, MD, PhD
Children’s Hospital
NCL Specialty Clinic
International Center of Lysosomal Storage Disorders (ICLD)
University Medical center Hamburg-­Eppendorf
Hamburg, Germany

A discussion about the early signs of CLN2 disease (new-­onset, unprovoked seizures and language delay) and how earlier diagnosis may benefit the child and their family.

References: 1. Schulz A et al. NCL diseases – clinical perspectives. Biochimica et Biophysica Acta. 2013;1832:1801-1806. 2. Mole SE et al. Correlations between genotype, ultrastructural morphology and clinical phenotype in the neuronal ceroid lipofuscinoses. Neurogenetics. 2005;6:107-126. 3. 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. 4. Williams RE et al. Expert opinion on the management of CLN2 disease. Poster session presented at: The 12th Annual WORLD Symposium; February – March 2016; San Diego, CA. 5. Schulz A et al. Neuronal ceroid lipofuscinosis-2 (CLN2) disorder, a type of Batten disease caused by TPP1 enzyme deficiency: current knowledge of the natural history from international experts. Poster session presented at: The Society for the Study of Inborn Errors of Metabolism (SSIEM) Annual Symposium; September 2015; Lyon, France. 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. Fietz M et al. Mol Genet Metab. 2016; 119:160–167 8. 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. 9. 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.