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

Abstract

Objective: Relative to youth with early-treated phenylketonuria (ETPKU), much less is known regarding the cognitive profile of adults with ETPKU. The present study aimed to address this gap by providing a comprehensive assessment of neuropsychological functioning among adults with ETPKU. Method: A sample of 40 adults with ETPKU (ages 18 – 36) and a demographically matched group of 32 healthy individuals without PKU participated. Participants completed a comprehensive neuropsychological battery including the NIH Toolbox, Wechsler Abbreviated Scale of Intelligence – Second Edition (WASI-II), Conners’ Continuous Performance Test (CPT-3), select subtests from the Weschler Adult Intelligence Scale – Fourth Edition (WAIS-IV) as well as several self-report measures of cognitive and psychoemotional functioning. Scores from these tests were combined to create cognitive composites reflecting overall task performance in the areas of verbal ability, visuospatial skills, executive functioning, motor skills, and processing speed. Results: No group differences were observed for full scale IQ or verbal ability. However, individuals with ETPKU demonstrated poorer performance on measures of executive functioning, processing speed, motor skills, and visuospatial skills as compared to the non-PKU group. Within the ETPKU group, recent blood phenylalanine levels (an indicator of metabolic control) were significantly correlated with performance across most cognitive domains and aspects of psychological functioning. Conclusions: Present findings suggest that the neuropsychological profile of adult ETPKU is characterized by circumscribed impairments in select cognitive domains. In addition, the results underscore the importance of maintaining metabolic control across the lifespan in individuals with ETPKU.

The relationship between working memory and anxiety in individuals with early treated phenylketonuria (PKU).

“…The groups did not differ significantly in anxiety; however, high anxiety was more common in the ETPKU group (53% of sample) than the non-PKU group (33%). Previous findings on the association between anxiety symptomatology and Phe levels have been equivocal, with some observing a relationship (e.g., Clacy et al, 2014; Clocksin et al, 2023; Waisbren et al, 2017) and others not (e.g., Brumm et al, 2004; Burton et al, 2013; Jahja et al, 2017; Weglage et al, 2000). Within this context, we found no relationship between current or historic Phe levels and anxiety symptomatology.…”

“…They reported the largest effect for WM-related symptoms/behaviors, with 19% of children and 29% of adults scoring in the "abnormally elevated" range on the associated scale. In another recent comprehensive study of neurocognitive functioning in adults with ETPKU, Clocksin et al (2023) found that ETPKU-related impairments in EF were most apparent on a computerized WM list sorting task (as compared to the other EF tasks that were administered). Within their ETPKU group, EF performance was also strongly correlated with recent metabolic control (as reflected by blood Phe levels).…”

Expert Consensus on the Long-Term Effectiveness of Medical Nutrition Therapy and Its Impact on the Outcomes of Adults with Phenylketonuria

“…Although childhood Phe remains the most important determinant of early and late neurocognitive outcomes, the limited effectiveness of MNT in the long term can still increase the risk for developing deficits in neurocognitive functioning in adulthood [ 15 , 37 , 39 , 41 , 42 , 46 , 47 , 148 , 149 ]. Even when controlling for historic Phe levels, adults were reported to experience cognitive difficulties in executive functioning, processing speed, motor skills and visuospatial skills, of which the severity correlated with concurrent blood Phe concentrations [ 37 , 148 , 150 ]. There is therefore no debate on the need for lifelong treatment to prevent these PKU-related cognitive symptoms.…”