Poster Presentation International Congress on Neuronal Ceroid Lipofuscinoses 2025

Adaptive Behavior in CLN3 disease and relationship to disease stage (#13)

Heather R Adams 1 , Erika F Augustine 1 2 , Marianna Pereira-Freitas 1 , Jennifer Vermilion 1 , Amy E Vierhile 1 , Jonathan W Mink 3
  1. University of Rochester Medical Center (UR Batten Center), Rochester, NEW YORK, United States
  2. Kennedy Krieger Institute, Baltimore, MD, USA
  3. independent consultant, Rochester, New York, USA

Background and Objectives. The CLN3 Staging System (CLN3SS) classifies CLN3 disease stage using diagnosis and incremental onset of three cardinal symptoms - vision loss, seizures, and loss of independent ambulation.  These symptoms impact daily functional independence, but the relationship between disease stage and broader functional abilities has not yet been explored. This study aimed to explore the association between adaptive function and disease stage as defined by the CLN3SS.

 

Methods. The relationship between Vineland-3 adaptive scores and CLN3SS score was analyzed in 30 individuals (14 males, 16 females) with genetically confirmed CLN3 disease.  Lower Vineland-3 score=worse adaptive function; Higher CLN3SS=later disease stage (range: 0-3). Analyses were performed on 94 assessments (1-6 Vineland-3 assessments per child).

 

Results. Mean age at most recent assessment=13.4 years old (SD=4.9, range=3.0–26.0 years). The Vineland-3 Adaptive Behavior Composite (ABC) was correlated with disease stage (F [1,3]=17.3, p<.00001). Post-hoc (Bonferroni) analyses revealed the mean score for Vineland-3 was significantly different between CLN3SS=3 and each earlier disease stage (each p < .00001). This relationship was borne out for Vineland-3 Domain-level scores (Communication, Daily Living Skills, Socialization) which are age-adjusted, reflecting performance compared to same-age peers. Individual subdomains (e.g., Expressive Language, etc.) can be described with Growth Scale Value (GSV) scores that map skill level without reference to age-expected abilities. Vineland-3 GSVs present a more nuanced picture, showing that for all subdomains, adaptive skills either increase or plateau from CLN3SS=0 to 2, only decreasing notably between Stage 2 to 3.

 

Conclusions. The metrics used to characterize changes in adaptive function leads to varying interpretations of change in skills over the course of disease progression. Use of GSV scores illuminates an ongoing balance between maturation/development and degeneration/loss until  affected individuals move into Stage 3 of disease (vision loss + seizures + loss of ambulation) when functional decline accelerates.

  1. 34. Vermilion J, Augustine E, Adams HR, Vierhile A, Lewin AB, Thatcher A, McDermott MP, O’Connor T, Kurlan R, van Wijngaarden E, Murphy TK, Mink JW. Tic disorders are associated with lower child and parent quality of life and worse family functioning. Pediatric Neurology. 2020. 105:48-54. doi: 10.1016/j.pediatrneurol.2019.12.003.