Subtle visuomotor deficits and reduced benefit from practice in early treated phenylketonuria

Introduction: Phenylketonuria (PKU) is a rare metabolic disease that causes slight-to-severe neurological symptoms. Slow performance has been observed in PKU but the influence of high-order (i.e., not purely motor) deficits and of temporary variations of the phenylalanine (Phe) level on this slowness has not been fully corroborated as yet. Response speed and the effect of motor practice during the performance of a visuomotor coordination task were measured, in a group of patients with early-treated phenylketonuria (ET PKU). Method: We compared the performance of a group of early-treated PKU patients with ages ranging from 11 to 25years and a control group of healthy volunteers on a computerized visuomotor task. Participants performed rapid movements towards one of five response buttons, as indicated by a visual stimulus that could appear in five different positions on a computer screen. The results of our visuomotor task were correlated with neurobiological data (Phe levels) and with neuropsychological measures of motor (finger tapping) and executive functions (Stroop task). Results: The ET PKU group showed slower responses than the control group. Furthermore, an absence of a practice effect (i.e., faster response times at the end of the study) was found in the PKU group but not in the control group. Our results also revealed that this absence of practice effect correlated with higher Phe levels on the testing day with respect to the average Phe level of the previous 12months and, although weakly, with performance on the Stroop task. Conclusions: This pattern of results indicates slower visuomotor performance and a less beneficial effect of practice in ET PKU. The correlations found among our visuomotor measures, the same-day Phe level, and the Stroop test may reflect the negative effects of dopamine reduction in brain areas involved in motor control, selective attention, and learning.