TY - JOUR
T1 - Long-term preservation of intellectual functioning in sapropterin-treated infants and young children with phenylketonuria
T2 - A seven-year analysis
AU - Waisbren, Susan
AU - Burton, Barbara K.
AU - Feigenbaum, Annette
AU - Konczal, Laura L.
AU - Lilienstein, Joshua
AU - McCandless, Shawn E.
AU - Rowell, Richard
AU - Sanchez-Valle, Amarilis
AU - Whitehall, Kaleigh B.
AU - Longo, Nicola
N1 - Funding Information:
This study and support in the process of manuscript development were funded by BioMarin Pharmaceutical Inc., Novato, CA, USA.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.
PY - 2021/2
Y1 - 2021/2
N2 - 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.
AB - 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.
KW - Intellectual functioning
KW - Phenylketonuria
KW - Sapropterin
UR - http://www.scopus.com/inward/record.url?scp=85099628599&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85099628599&partnerID=8YFLogxK
U2 - 10.1016/j.ymgme.2021.01.001
DO - 10.1016/j.ymgme.2021.01.001
M3 - Article
C2 - 33485801
AN - SCOPUS:85099628599
VL - 132
SP - 119
EP - 127
JO - Molecular Genetics and Metabolism
JF - Molecular Genetics and Metabolism
SN - 1096-7192
IS - 2
ER -