Oral Presentation International Congress on Neuronal Ceroid Lipofuscinoses 2025

A Timeline of Symptom Onset and Disease Progression in CLN3 Disease (127687)

Ineka T Whiteman 1 2 3 , Anthony L Cook 4 , Erika F Augustine 5 , Aidan D Bindoff 4 , Alexandra M Johnson 6 , Heather L Mason 7 , Jonathan W Mink 8 , John R Østergaard 9 , Angela Schulz 10 11 , Jennifer Vermilion 12 , Amy Vierhile 12 , Heather R Adams 12
  1. BDSRA Australia, Diddillibah, QLD, Australia
  2. BDSRA Foundation, Columbus, OH, USA
  3. Beyond Batten Disease Foundation, Austin, TX, USA
  4. Wicking Dementia Research and Education Centre, University of Tasmania, Hobart, TAS, Australia
  5. Kennedy Krieger Institute, Baltimore, MD, USA
  6. Department of Neurology, Sydney Children’s Hospital, University of New South Wales, Randwick, NSW, Australia
  7. Coufetery Comms, Paris, France
  8. Independent Consultant, Pittsford, NY, USA
  9. Centre for Rare Diseases, Aarhus University Hospital, Aarhus, Denmark
  10. Children’s Hospital, , University Medical Center Hamburg-Eppendorf , Hamburg, Germany
  11. German Center for Child and Adolescent Health (DZKJ), Hamburg, Germany
  12. Department of Neurology, University of Rochester Medical Center, Rochester, NY, USA

Symptom onset in CLN3 disease generally occurs in the first decade of life, progressing in severity, with death typically occurring in the third decade of life. We conducted a literature review to analyse onset of core symptoms and chronological progression based on natural history data. We aimed to better understand the disease progression timeline, which remains a notable unmet need for the patients, families, and the medical community.

A literature review was undertaken in June 2024 using PubMed and a pre-defined search strategy focused on CLN3 disease and publications where ages of symptom onset were provided in cohorts of n=15 or more. Data reported as mean ± range were transformed to mean and standard deviation. Weighted mean age at onset and standard deviations were calculated for each symptom and then compared using ANOVA.

We identified nine studies that evaluated one or more clinical symptoms of CLN3 disease. In total, 423 discrete patients ages 4-39 years were reported. Thirteen common and associated symptoms and a weighted average age at onset and weighted standard deviation were (in years): vision loss (6.0±1.7), behavioural changes (8.5±3.9), cognitive decline (9.3±3.1), seizures (10.2±3.0), sleep disturbance (11.0±6.1), motor decline (11.0±3.8), complete blindness (11.4±3.6), speech/language impairment (12.7±4.8), Parkinsonian gait (14.1±2.5), cardiac manifestations (17.8±4.4), loss of independent walking (19.5±3.2), feeding difficulties requiring gastric tube (22.0±1.6), and death (22.4±4.4).

This comprehensive summary of available natural history data identified 13 common and associated symptoms of CLN3 disease, including core symptoms of vision loss, seizures, cognitive and motor decline, and behaviour changes, with their chronological onset and progression. This summary provides much-needed practical and anticipatory guidance to those involved in caring for people with CLN3 disease and serves to highlight the critical importance of collecting globally standardised, quantifiable, longitudinal data for advancing therapeutic development.