Motor function impairment is an early sign of CLN3 disease.

ABSTRACT

OBJECTIVE: To delineate timing of motor decline in CLN3 disease. METHODS: Motor function, assessed by the 6-Minute Walk Test (6MWT), was evaluated repeatedly in 15 patients with CLN3 disease, resulting in 65 test results and during one occasion in 2 control cohorts. One control cohort (n = 14) had isolated visual impairment; a second cohort (n = 12) exhibited visual impairment in combination with neurologic impairments. Based on 6MWT reference values in healthy sighted children, z scores of 6MWT results in patients with CLN3 disease and control cohort individuals were calculated. 6MWT results were correlated with age-including multilevel modeling analysis allowing assessment of imbalanced repeated measurements-and with Unified Batten Disease Rating Scale (UBDRS) scores. RESULTS: In CLN3 disease, 6MWT scores were already impaired from first testing near diagnosis (mean z scores of -3.6 and -4.7 at 7 and 8 years of age, respectively). Afterwards, 6MWT scores continuously declined with age (r = -0.64, p < 0.0001) and with increasing UBDRS scores (r = -0.60, p = 0.0001), confirming correlation with disease progression. The decrease was more pronounced at a later age, as shown by the nonlinear multilevel model for 6MWT results in CLN3 disease (y = 409.18 - [0.52 × age2]). In contrast, an upward trend of 6MWT scores with age was observed in the control cohort with isolated visual impairment (r = 0.56; p = 0.04) similar to healthy, sighted children. The control cohort with additional neurologic impairments displayed a slightly decreased 6MWT walking distance independent of age. CONCLUSIONS: The 6MWT unveils early onset of motor decline in CLN3 disease.