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Neuropsychiatric Function Improvement in Pediatric Patients with Phenylketonuria
Journal article   Open access   Peer reviewed

Neuropsychiatric Function Improvement in Pediatric Patients with Phenylketonuria

Mitzie L. Grant, Elaina R. Jurecki, Shawn E. McCandless, Stephen M. Stahl, Deborah A. Bilder, Amarilis Sanchez-Valle and David Dimmock
The Journal of pediatrics, v 260, 113526
01 Sep 2023
PMID: 37263523
url
https://doi.org/10.1016/j.jpeds.2023.113526View
Published, Version of Record (VoR) Open

Abstract

ADHD neuropsychiatric phenylalanine phenylketonuria PKU sapropterin
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.

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Pediatrics
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