Background: CLN2 disease is an autosomal recessively inherited storage disorder caused by deficient activity of the lysosomal enzyme tripeptidyl peptidase 1 (TPP1). The late infantile phenotype is characterized by rapid psychomotor decline and epilepsy. Early diagnosis and exact knowledge of the natural clinical course are important for evaluating experimental therapies. Aims: (1) To analyze time of onset and character of first symptoms, (2) to provide quantitative longitudinal data on motor and language function in a cohort of 58 CLN2 patients, using an established clinical rating scale (Steinfeld et al 2002). Results: (1) Mean age at symptom onset and diagnosis were 35 and 56 months, respectively, indicating diagnosis occurred on average 21 months after onset of first symptoms, reported as seizures (70%), loss of language (57%) or motor abilities (40%). However, a systematic review of early language development in 36 patients revealed that 83% had a significant delay in language development preceding the onset of other symptoms. (2) Our cohort showed a highly homogeneous, rapid decline in motor-language summary scores from normal (score 6) to no function (score 0), which occurred over ~36 months with a mean rate of decline of −1.9 units per year. Conclusion: This study represents the largest set of quantitative longitudinal data on the natural history of CLN2 disease to date. Delayed language acquisition frequently precedes the onset of more typical symptoms. The course of disease is highly predictable. Our data may therefore serve as valid controls for the evaluation of effects of experimental therapies.
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Nickel et al. (2016) studied this question.