Hamburg iNCL Scale: A New Tool for the Quantitative Description of Disease Progression in Infantile CLN1 Patients

Background/Purpose: 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.

Methods: We followed up a cohort of 13 infantile CLN1 patients (3 females, 10 males) longitudinally. Mean age at symptom onset was 11.0 months (SD 3.9). First symptom was motor developmental delay in 12 patients, followed by language developmental delay. None of these patients ever achieved the ability to walk without support and only 5 patients learned single words. Since this low level of maximum developmental function differs significantly from all other NCL phenotypes, established rating scales couldn´t be applied and a new adapted rating scale was developed. Rating three main functional categories (gross motor function, fine motor function, and expressive language) and six clinically and functionally meaningful categories (communication/interaction, visual attention, irritability/agitation, seizures, sleep, and feeding), loss of function can be scored retrospectively and prospectively.

Results: Our longitudinal data showed that mean age of first regression was 19.6 months (SD: 2.0) for gross motor function and 18.2 months (SD: 2.2) for expressive language function. Total loss of gross motor function occurred at a mean age of 31.3 month (SD: 7.3), total loss of expressive language at mean age of 23.9 month (SD: 5.5).

Conclusion: We have developed a clinical scoring system for infantile NCL patients for robust quantitative description of disease progression. On the basis of our results, effects of future therapeutic interventions may be evaluated.

No conflict of interest has been declared by the author(s).

Publication History

Article published online:
28 October 2021