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 drugs 4
  • Myoclonus—both epileptic and non-epileptic—is the most predominant feature5

The prominence of seizures often results in an epilepsy syndrome diagnosis without pursuing the aetiology of the seizures. This often results 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 a majority of patients8

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

  • Criteria for identifying early language delay:
    • 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 caregivers about early language development, even if current abilities appear normal.7,8
  • Less than 25% of children aged 2 to 4 seeking medical attention with new onset, unprovoked seizures, also had language delay9

Not all children will have early language delay—some children may exhibit ataxia or other developmental delays as early symptoms.10

When children aged 2 to 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 Specialist Clinic
International Centre for Lysosomal Storage Disorders (ICLD)
University Medical Centre 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, Kohlschütter A, Mink J, Simonati A, Williams R. NCL diseases – clinical perspectives. Biochimica et Biophysica Acta. 2013;1832:1801-1806. 2. Mole SE, Williams RE, and Goebel HH. Correlations between genotype, ultrastructural morphology and clinical phenotype in the neuronal ceroid lipofuscinoses. Neurogenetics. 2005;6:107-126. 3. Pérez-Poyato MS, Marfa MP, Abizanda IF, 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, Adams HR, Blohm M, 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, Cohen-Pfeffer JL, Crystal R, 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, Cooper JD, Davidson BL, 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, Giugliani R, AlSayed M, et al. Expert recommendations for the laboratory diagnosis of neuronal ceroid lipofuscinosis type 2 (CLN2 disease): diagnostic algorithm and best practice guidelines for a timely diagnosis. Poster session presented at: The 12th Annual WORLD Symposium; February – March 2016; San Diego, CA. 8. Nickel M, Jacoby D, Lezius S, 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. Åndell E, Tomson T, Carlsson S, et al. The incidence of unprovoked seizures and occurrence of neurodevelopmental comorbidities in children at the time of their first epileptic seizure and during the subsequent six months. Epilepsy Res. 2015;113:140-150. 10. Worgall S, Sondhi D, Hackett NR, 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.