Oral Presentation International Congress on Neuronal Ceroid Lipofuscinoses 2025

Analysis of longitudinal natural history data in infantile CLN1 patients from two independent international cohorts using the Hamburg iCRS scale (126469)

Miriam Nickel 1 , Johannes Finter 1 , Christoph Schwering 1 , Lena Westermann 1 , Susanne Lezius 2 , Angela Schulz 1 3 , Minna Laine 4
  1. University Children’s Hospital, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
  2. Department of Biometrics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
  3. German Center for Child and Adolescent Health (DZKJ), partner site Hamburg, Hamburg, Germany
  4. Department of Pediatric Neurology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland

Neuronal ceroid-lipofuscinosis type 1 (CLN1) disease is caused by deficiency of the lysosomal enzyme palmitoyl-protein thioesterase 1 (PPT1). The classic infantile phenotype in CLN1 represents the most rapidly progressive form among all NCL phenotypes and presents with developmental delay.

Natural history data from 21 genotype-confirmed infantile CLN1 patients from two independent international cohorts, the German Hamburg data set (N = 14) and the Finnish Helsinki data set (N = 7) were analyzed using the newly developed Hamburg iCRS (infantile clinical rating scale). It consists of three main functional categories, gross motor, fine motor, and expressive language function. Each category is scored 3 (normal function), 2 (developmental delay), 1 (first regression), and 0 (total loss of function). In addition, six clinically meaningful categories such as communication/interaction, visual attention, irritability/agitation, seizures, sleep, and feeding are each rated 1 (age appropriate) or 0 (pathologic).

Comparative analysis of longitudinal data of the two cohorts showed similar age ranges regarding onset of regression: mean age of first regression for gross motor function, expressive language, and fine motor function was 18.9 months (SD 2.7), 18.2 months (SD 2,5), and 18.9 months (SD 2.2), respectively in the Hamburg cohort. In comparison, corresponding mean ages of first regression in the Helsinki cohort were 13.4 months (SD 5,8), 16.3 months (SD 2.1), and 18 months (SD 3,2).

Similarly, mean ages when pathologic changes were reported in the six add-on categories were very close with a mean difference between cohorts of 4.1 months, 4.2 months, 3.4 months, 3.4 months, 1.7 months and 2 months for communication/interaction, visual attention, irritability/agitation, seizures, sleep, and feeding.

In conclusion, this longitudinal analysis of two independent international cohorts with infantile CLN1 disease confirms that disease course is very homogeneous. Data from this study might serve as valid tools to determine efficacy of experimental therapies.