Gait deviations in adolescent patients with Wilson disease and their possible connections with biochemical markers:...

The study aims to evaluate the gait pattern of Wilson Disease adolescents, receiving pharmacological treatment, without clinical signs of gait problems, with instrumented gait analysis. The gait changes could be the first signs of neurological manifestations, providing information about which patients are at greater risk of developing neurological problems. Another aim of the paper was to find possible relationships between gait disturbances and biochemical markers. Twenty-seven patients underwent gait analysis with the VICON system. Captured data were processed and averaged. From them, the Gait Variable Scores and Gait Profile Score were calculated to assess the deviation from normal gait. The following biochemical parameters were included in the analysis: ALT, AST, GGTP, bilirubin, INR, and an abdominal ultrasound describing liver and spleen size. Additionally, a fibroscan measurement was performed to obtain information about liver stiffness (E value) and steatosis (CAP value). The neurological assessment was based on a review of school performance, tremor, walking, and writing problems. In all patients, the scores assessing global gait pattern and knee kinematics were increased, and in the majority of them, also the score of the ankle joint. Cluster and discriminant analysis showed that biochemical indicators of liver injury (ALT, E, and CAP value) were strong predictors of walking disturbances.

The main finding of this study indicates that clinical assessment could detect abnormalities only when they are in a relatively advanced stage. It is not sensitive to the early signs of neurological problems, which could be picked up by the instrumented gait analysis.

• Wilson disease is a rare genetic disorder affecting copper metabolism. • Liver problems are its first clinical manifestations. • It is accepted that neurological manifestations in Wilson disease patients have onset between 20 and 30 years of age.

• First subtle gait pattern changes are present in adolescents, despite their pharmacological treatment. • These changes can be detected by instrumented gait analysis. • The deviations mainly concern the knee and ankle joints. • The major indicators of liver injury (ALT, E, and CAP value) were strong predictors of walking disturbances.