Introduction of sapropterin dihydrochloride as standard of care in patients with phenylketonuria

Hilary J Vernon, C. B. Koerner, M. R. Johnson, A. Bergner, Ada Hamosh

Research output: Contribution to journalArticle

Abstract

Sapropterin dihydrochloride, a synthetic, stable form of the tetrahydrobiopterin cofactor of phenylalanine hydroxylase, has been shown to reduce plasma phenylalanine (Phe) levels in a significant portion of patients with phenylketonuria (PKU). When we undertook introducing this medication to our PKU clinic population, the challenges of recalling and reconnecting with a variably treated and variably compliant patient population became apparent. We offered a trial of sapropterin to all of our clinic patients with PKU. In order to determine responsiveness, we used a two tier dose escalation protocol. After diet records were taken, and baseline plasma Phe levels were established, a 7-day trial of sapropterin at 10 mg/kg/day was started. At day 8, plasma phenylalanine levels were measured. Patients were considered to be responders if they had a 30% reduction in plasma Phe. If they did not respond, the dose of sapropterin was increased to 20 mg/kg/day, and levels were rechecked again in 8 days. Patients who were not responders at this time continued sapropterin for a total of 30 days and had Phe levels checked one last time. Patients who were responders and who were on a Phe-restricted diet underwent gradual liberalization of their diet to the maximum tolerated natural protein intake while still maintaining plasma levels in the acceptable treatment range of 120-360 μmol/L. In our population, 36/39 patients with hyperphenylalaninemia (HPA) who were offered a trial of sapropterin elected to start sapropterin. Five of 36 patients were non-adherent with diet records and/or medication doses and we were unable to determine if they were responders. We were unable to categorize 2 of 31 of the patients who completed the trial as responders due to dietary issues, though they were probably responders. Of the 29 patients who completed the sapropterin trial and we could categorize, 18/29 (62%) were determined to be responders. Patients were classified based on their off-diet diagnostic plasma phenylalanine levels as classical PKU (>1200 μmol/L) and variant PKU (>400 and

Original languageEnglish (US)
Pages (from-to)229-233
Number of pages5
JournalMolecular Genetics and Metabolism
Volume100
Issue number3
DOIs
StatePublished - Jul 2010

Fingerprint

Phenylketonurias
Standard of Care
Phenylalanine
Nutrition
Plasmas
Diet Records
Diet
sapropterin
Plasma diagnostics
Population

Keywords

  • Phenylketonuria
  • Sapropterin dihydrochloride
  • Tetrahydrobiopterin

ASJC Scopus subject areas

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

Cite this

Introduction of sapropterin dihydrochloride as standard of care in patients with phenylketonuria. / Vernon, Hilary J; Koerner, C. B.; Johnson, M. R.; Bergner, A.; Hamosh, Ada.

In: Molecular Genetics and Metabolism, Vol. 100, No. 3, 07.2010, p. 229-233.

Research output: Contribution to journalArticle

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abstract = "Sapropterin dihydrochloride, a synthetic, stable form of the tetrahydrobiopterin cofactor of phenylalanine hydroxylase, has been shown to reduce plasma phenylalanine (Phe) levels in a significant portion of patients with phenylketonuria (PKU). When we undertook introducing this medication to our PKU clinic population, the challenges of recalling and reconnecting with a variably treated and variably compliant patient population became apparent. We offered a trial of sapropterin to all of our clinic patients with PKU. In order to determine responsiveness, we used a two tier dose escalation protocol. After diet records were taken, and baseline plasma Phe levels were established, a 7-day trial of sapropterin at 10 mg/kg/day was started. At day 8, plasma phenylalanine levels were measured. Patients were considered to be responders if they had a 30{\%} reduction in plasma Phe. If they did not respond, the dose of sapropterin was increased to 20 mg/kg/day, and levels were rechecked again in 8 days. Patients who were not responders at this time continued sapropterin for a total of 30 days and had Phe levels checked one last time. Patients who were responders and who were on a Phe-restricted diet underwent gradual liberalization of their diet to the maximum tolerated natural protein intake while still maintaining plasma levels in the acceptable treatment range of 120-360 μmol/L. In our population, 36/39 patients with hyperphenylalaninemia (HPA) who were offered a trial of sapropterin elected to start sapropterin. Five of 36 patients were non-adherent with diet records and/or medication doses and we were unable to determine if they were responders. We were unable to categorize 2 of 31 of the patients who completed the trial as responders due to dietary issues, though they were probably responders. Of the 29 patients who completed the sapropterin trial and we could categorize, 18/29 (62{\%}) were determined to be responders. Patients were classified based on their off-diet diagnostic plasma phenylalanine levels as classical PKU (>1200 μmol/L) and variant PKU (>400 and",
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