Motor function impairment is an early sign of CLN3 disease

Abstract

ObjectiveTo delineate timing of motor decline in CLN3 disease.MethodsMotor 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.ResultsIn 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.ConclusionsThe 6MWT unveils early onset of motor decline in CLN3 disease.