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

Susan Waisbren, Barbara K. Burton, Annette Feigenbaum, Laura L. Konczal, Joshua Lilienstein, Shawn E. McCandless, Richard Rowell, Amarilis Sanchez-Valle, Kaleigh B. Whitehall, Nicola Longo*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)119-127
Number of pages9
JournalMolecular Genetics and Metabolism
Issue number2
StatePublished - Feb 2021


  • Intellectual functioning
  • Phenylketonuria
  • Sapropterin

ASJC Scopus subject areas

  • Genetics
  • Endocrinology
  • Molecular Biology
  • Biochemistry
  • Endocrinology, Diabetes and Metabolism


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