Neuropsychiatric Function Improvement in Pediatric Patients with Phenylketonuria

• Published in: The Journal of pediatrics 2023-09, Vol.260, p.113526-113526, Article 113526
• Main Authors: Grant, Mitzie L., Jurecki, Elaina R., McCandless, Shawn E., Stahl, Stephen M., Bilder, Deborah A., Sanchez-Valle, Amarilis, Dimmock, David
• Format: Article
• Language: English
• Subjects: ADHD; neuropsychiatric; phenylalanine; phenylketonuria; PKU; sapropterin
• ISSN: 0022-3476; 1097-6833
• DOI: 10.1016/j.jpeds.2023.113526

To evaluate effects of sapropterin dihydrochloride on blood phenylalanine (Phe) and symptoms of neuropsychiatric impairment in children and adolescents with phenylketonuria (PKU). PKU subjects 8-17 years of age (n = 86) were randomized to double-blind treatment with sapropterin (n = 43) or placebo (n = 43) for 13 weeks, then all received open-label sapropterin therapy for an additional 13 weeks. Blood Phe and symptoms of inattention, hyperactivity/impulsivity (Attention-Deficit/Hyperactivity Disorder Rating Scale IV [ADHD RS-IV]), executive functioning (Behavior Rating Inventory of Executive Function), depression (Hamilton Rating Scale for Depression), and anxiety (Hamilton Rating Scale for Anxiety) were assessed. Following the 13-week randomization phase, the sapropterin and placebo groups had mean changes in blood Phe of −20.9% and +2.9%, respectively. Corresponding least square mean differences in ADHD RS-IV scores were significantly greater for the sapropterin vs the placebo group: Total (−3.2 points, P = .02), Inattention subscale (−1.8 points, P = .04), and Hyperactivity/Impulsivity subscale (−1.6 points, P = .02). Forest plots favored sapropterin treatment over placebo for all ADHD RS-IV and Behavior Rating Inventory of Executive Function indices. There were no significant differences in reported problems with attention or executive function between the 2 groups at baseline or at week 26 following the 13-week open-label treatment period. Anxiety and depression scores did not differ significantly between cohorts at any time. Sapropterin was well tolerated, with a favorable safety profile. Sapropterin reduced blood Phe and was associated with significant improvement in parent-reported symptoms of inattention, hyperactivity/impulsivity, and executive functioning in children and adolescents with PKU. ClinicalTrials.gov, NCT01114737. Registered 27 April 2010, https://clinicaltrials.gov/ct2/show/NCT01114737.