Neuropsychiatric Function Improvement in Pediatric Patients with Phenylketonuria - 08/09/23
, Shawn E. McCandless, MD 3, Stephen M. Stahl, MD, PhD 4, Deborah A. Bilder, MD 5, Amarilis Sanchez-Valle, MD 6, David Dimmock, MD 7Abstract |
Objective |
To evaluate effects of sapropterin dihydrochloride on blood phenylalanine (Phe) and symptoms of neuropsychiatric impairment in children and adolescents with phenylketonuria (PKU).
Study design |
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.
Results |
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.
Conclusions |
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.
Trial registration |
ClinicalTrials.gov, NCT01114737. Registered 27 April 2010, NCT01114737.
Le texte complet de cet article est disponible en PDF.Keywords : ADHD, neuropsychiatric, phenylalanine, phenylketonuria, PKU, sapropterin
Abbreviations : ACMG, ADHD, ADHD RS-IV, AE, BRIEF, BRIEF-BRI, BRIEF-GEC, BRIEF-MI, HAM-A, HAM-D, LS, PAH, Phe, PKU
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Vol 260
Article 113526- septembre 2023 Retour au numéro
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