Systematic Review and Meta-Analysis of Neuropsychiatric Symptoms and Executive Functioning in Adults With Phenylketonuria.

This systematic review and meta-analysis (MA) investigates the impact of elevated blood phenylalanine (Phe) on neuropsychiatric symptoms in adults with phenylketonuria (PKU). The meta-analysis of PKU is challenging because high-quality evidence is lacking due to the limited number of affected individuals and few placebo-controlled, double-blind studies of adults with high and low blood Phe. Neuropsychiatric symptoms associated with PKU exceed general population estimates for inattention, hyperactivity, depression, and anxiety. High Phe is associated with an increased prevalence of neuropsychiatric symptoms and executive functioning deficits whereas low Phe is associated with improved neurological performance. Findings support lifelong maintenance of low blood Phe.

An Adaptation of the Profile of Mood States for Use in Adults With Phenylketonuria

Abstract Adults with phenylketonuria (PKU) experience disturbances in mood. This study used qualitative and quantitative techniques to adapt the 65-item Profile of Mood States (POMS) for the assessment of key mood domains in adults with PKU. First, cognitive interviews on 58 POMS items (excluding 7 Friendliness domain items) among 15 adults and adolescents (age ≥16 years) with PKU were conducted to eliminate items poorly understood or considered irrelevant to PKU; 17 items were removed. Next, the remaining POMS items were quantitatively examined (Mokken scaling and Rasch analysis) in 115 adult patients with PKU. An additional 21 items were removed iteratively, resulting in the 20-item draft PKU-POMS. Finally, the psychometric properties of the draft PKU-POMS were examined. The instrument displayed strong psychometric properties (reliability, validity, and responsiveness) over 6 domains (Anxiety, Depression, Anger, Activity, Tiredness, and Confusion) and all items were well understood in the final cognitive interviews with 10 adults with PKU.

Assessing the Content Validity of the Investigator-Rated ADHD Rating Scale Version IV Instrument Inattention Subscale for Use in Adults With Phenylketonuria

Abstract Content validity of the 18-item Investigator-Rated Attention-Deficit Hyperactivity Disorder (ADHD) Rating Scale IV (I-ADHD RS-IV) with adult prompts was investigated using qualitative interviews of US clinicians who had prior experience rating adults with phenylketonuria (PKU) using the I-ADHD RS-IV. Fourteen qualitative interviews were conducted to obtain key symptom experiences of adults with PKU and assessed the relevance, clarity, and administration of the I-ADHD RS-IV. Participants (n = 13, 92.9%) endorsed the inattention symptoms as key experiences by adults with PKU and endorsed the instrument as fit for purpose for adults with PKU. Participants generally reported low frequencies of occurrence for the 9 I-ADHD RS-IV hyperactivity/impulsivity items. Despite some clinicians' concerns for the lack of patient self-awareness, the participants reported no difficulty selecting a rating on these items. This in-depth study of the content validity of the I-ADHD RS-IV provides evidence that this clinician-reported instrument captures the severity of important inattention symptoms in adults with PKU.