Long-term preservation of intellectual functioning in sapropterin-treated infants and young children with phenylketonuria: A seven-year analysis.

Sapropterin dihydrochloride has been approved for the treatment of hyperphenylalaninemia in infants and young children with phenylketonuria (PKU). Sapropterin can reduce phenylalanine (Phe) levels in tetrahydrobiopterin (BH4)-responsive patients, potentially preventing the intellectual impairment caused by elevated Phe levels. The long-term effect of sapropterin on intellectual functioning was assessed using the Full-Scale Intelligence Quotient (FSIQ) in 62 children who began treatment before the age of 6 years. Over each 2-year interval, the estimate of mean change in FSIQ was -0.5768 with a lower limit of the 95% confidence interval (CI) of -1.60. At the end of the follow-up period (Year 7), the least squares mean estimate of the change in FSIQ from baseline was 1.14 with a lower limit of the 95% CI of -3.53. These lower limits were both within the clinically expected variation of 5 points. During the whole study period, mean blood Phe levels remained within the American College of Medical Genetics (ACMG) target range of 120-360 μmol/L. In addition, height, weight, and head circumference were maintained within normal ranges throughout follow-up, as defined by growth charts from the World Health Organization (WHO) and Centers for Disease Control and Prevention (CDC) for children below and above the age of 24 months, respectively. All patients (n = 65) enrolled in this study experienced at least one adverse event, as expected from previous studies. In conclusion, long-term use of sapropterin in individuals with PKU helps to control blood Phe, preserve intellectual functioning, and maintain normal growth in BH4-responsive children who initiated treatment between the ages of 0 to 6 years.
Competing Interests: Declaration of Competing Interest BKB has received personal fees from BioMarin outside the submitted work. AF has received payments from BioMarin during the conduct of the study. SEM and NL have received grants and personal fees from BioMarin during the conduct of the study. AS-V is a principal investigator for several BioMarin clinical trials, has received payment from serving in advisory boards funded by BioMarin, and participated in a speakers bureau for BioMarin. SW has received consulting fees from BioMarin during the conduct of the study, and from Homology, Pfizer and Synlogic outside the submitted work. JL, KBW, and RR are employees of BioMarin Pharmaceutical Inc. LLK has nothing to declare.
(Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)