Motor control and learning in individuals with early-treated phenylketonuria.

Abstract

Objective: Although past studies have documented motor control impairments in individuals with early-treated phenylketonuria (ETPKU), much less is known regarding motor learning in ETPKU. The goal of the present study was to advance our understanding on this front. Method: We isolated and examined motor kinematics associated with the learning of a rapid aimed limb movement in a sample of 40 individuals (13-34 years of age) with ETPKU and a matched comparison group of 40 individuals without phenylketonuria (PKU). Indices of motor learning included overall movement duration as well as the relative proportion of movement time devoted to ballistic and corrective submovements. (Note that practice of motor movements in nonclinical populations is associated with, not only improvements in overall speed, but also reduction in the proportion of movement time devoted to corrective submovements relative to an initial ballistic submovement.) Results: A group-by-time interaction was found. With practice, the non-PKU group showed a significant reduction in the proportion of movement time devoted to the corrected (as compared to the ballistic) submovement. A similar change was not observed for the ETPKU group. In addition, within the ETPKU group, the rate of improvement in total movement duration was correlated with recent blood phenylalanine levels (an indicator of treatment adherence). Conclusions: Motor learning is adversely affected in individuals with ETPKU. Further investigation into the behavioral and neural mechanisms of motor learning in ETPKU will advance our understanding of the etiologic basis for this disruption as well as how it relates to the broader neurocognitive profile of ETPKU.

Management of early treated adolescents and young adults with phenylketonuria: Development of international consensus recommendations using a modified Delphi approach

“…Although anxiety, depression, and impaired executive functioning were deemed most important by the expert panel, screening should not be limited to these three areas of concern. Assessment of neurocognitive impairments in processing speed, sustained attention, fine motor skills, and expressive language, as well as other possible mental health conditions, such as panic attacks and psychosis, should also be considered [2,34,[36][37][38][39][40][41][42][43].…”

“…In addition, the expert panel recommends to perform early screening of fine-motor speed or visual-motor skills, using measures such as the Purdue Pegboard, Nine-Hole Peg, and Bruininks-Oseretsky Test of Motor Proficiency. Although more research is needed and there remains much uncertainty, impairments in these skills could be a first indication of the presence of underlying biochemical and/or structural brain disruptions in patients with PKU and indirectly impact other areas of development, such as learning and independent living skills [38][39][40]46,[71][72][73].…”

A comprehensive assessment of neurocognitive and psychological functioning in adults with early-treated phenylketonuria

“…This finding was driven primarily by group differences on measures of fine motor skills (e.g., grooved pegboard and simple pegboard) more so than those assessing gross motor ability (e.g., grip strength, walk endurance). The presence of disruptions in fine motor control has been widely reported in past studies of both children and adults with ETPKU (for reviews, see Moyle et al, 2007;Christ et al, 2021). Recent research from Christ et al, (2021) suggests that disruptions in motor learning likely contribute to the observed fine motor difficulties.…”

“…The presence of disruptions in fine motor control has been widely reported in past studies of both children and adults with ETPKU (for reviews, see Moyle et al, 2007;Christ et al, 2021). Recent research from Christ et al, (2021) suggests that disruptions in motor learning likely contribute to the observed fine motor difficulties. In addition, neurological studies in ETPKU have identified structural and/or functional disruptions in several brain regions (e.g., prefrontal cortex, parietal cortex, basal ganglia, cerebellum) known to play an important role in fine motor control and learning (Bodner et al, 2012;Christ et al, 2016Christ et al, , 2021Aldridge et al, 2020).…”

“…Most recent phe level on record as well as mean phe level for the year preceding study participation were calculated. As described previously (Christ et al, 2021), the index of dietary control (the mean of all half-year median phe levels) was computed for early childhood (0-5 years), middle childhood (6-11 years), adolescence (12-17 years), adulthood (18þ years), and lifetime (0-present). See Supplementary materials for more details.…”