Introduction. The Neuronal Ceroid Lipofusinoses (NCLs) comprise over 10 different inherited, fatal lysosomal storage diseases of childhood. Caused by mutations in different genes, the NCLs have several features in common including vision loss, epilepsy, progressive dementia, and motor problems. Some studies suggest that NCL forms differ by type of movement disorder, but this has not been evaluated quantitatively.

Methods. The Unified Batten Disease Rating Scale was used to assess age at onset of movement disorders and type of movement disorder.  The scale includes assessment of tone, bradykinesia, tremor at rest and with action, chorea, myoclonus, tics, dystonia, dysmetria, postural instability, and gait disorder.  Parkinsonism was rated by adding the tone, bradykinesia, tremor at rest, postural instability, and gait scores. Annual evaluations were performed over a 12-year period. Change in symptom severity over time was determined.

Results. Evaluations were performed in 93 individuals with CLN3 mutations (Juvenile NCL) and 12 individuals with CLN2 mutations (Late Infantile NCL).  The mean age at onset of motor impairment was 11.3 years in CLN3 and 3.5 years in CLN2. Parkinsonism was the predominant movement disorder in CLN3 disease whereas myoclonus and ataxia were predominant in CLN2 disease.

Conclusion. CLN2 and CLN3 manifest different types of movement disorder that localize to different systems in the brain, suggesting selective vulnerability of different neuron types in different forms of NCL. Our findings have important implications for understanding the pathobiology and for targeting therapy in the different forms of NCL.