title: Sapropterin dihydrochloride use in pregnant women with phenylketonuria: an interim report of the PKU MOMS sub-registry.
abstract: For pregnant women with phenylketonuria (PKU), maintaining blood phenylalanine (Phe)<360μmol/L is critical due to the toxicity of elevated Phe to the fetus. Sapropterin dihydrochloride (sapropterin) lowers blood Phe in tetrahydrobiopterin (BH4) responsive patients with PKU, in conjunction with a Phe-restricted diet, but clinical evidence supporting its use during pregnancy is limited. As of June 3, 2013, the Maternal Phenylketonuria Observational Program (PKU MOMS) sub-registry contained data from 21 pregnancies - in women with PKU who were treated with sapropterin either before (N=5) or during (N=16) pregnancy. Excluding data for spontaneous abortions (N=4), the data show that the mean of median blood Phe [204.7±126.6μmol/L (n=14)] for women exposed to sapropterin during pregnancy was 23% lower, and had a 58% smaller standard deviation, compared to blood Phe [267.4±300.7μmol/L (n=3)] for women exposed to sapropterin prior to pregnancy. Women on sapropterin during pregnancy experienced fewer blood Phe values above the recommended 360μmol/L threshold. When median blood Phe concentration was <360μmol/L throughout pregnancy, 75% (12/16) of pregnancy outcomes were normal compared to 40% (2/5) when median blood Phe was >360μmol/L. Severe adverse events identified by the investigators as possibly related to sapropterin use were premature labor (N=1) and spontaneous abortion (N=1) for the women and hypophagia for the offspring [premature birth (35w4d), N=1]. One congenital malformation (cleft palate) of unknown etiology was reported as unrelated to sapropterin. Although there is limited information regarding the use of sapropterin during pregnancy, these sub-registry data show that sapropterin was generally well-tolerated and its use during pregnancy was associated with lower mean blood Phe. Because the teratogenicity of elevated maternal blood Phe is without question, sapropterin should be considered as a treatment option in pregnant women with PKU who cannot achieve recommended ranges of blood Phe with dietary therapy alone.
authors.affiliation: Washington University School of Medicine, One Children's Place, NWT 9th Floor, St. Louis, MO 63110, USA.
authors.forename: Dorothy K
authors.initials: DK
authors.lastname: Grange
authors.affiliation: University of Missouri Health Care, One Hospital Drive, University of Missouri, Columbia, MO 65212, USA.
authors.forename: Richard E
authors.initials: RE
authors.lastname: Hillman
authors.affiliation: Ann and Robert H. Lurie Children's Hospital of Chicago, 225 E. Chicago Ave., Box #59, Chicago, IL 60611-2605, USA.
authors.forename: Barbara K
authors.initials: BK
authors.lastname: Burton
authors.affiliation: Los Angeles County & University of Southern California Medical Center, 1801 Marengo Street, Rm 1G-24, Los Angeles, CA 90033, USA.
authors.forename: Shoji
authors.initials: S
authors.lastname: Yano
authors.affiliation: University of Pittsburgh School of Medicine, Children's Hospital of Pittsburgh, 4401 Penn Ave, Pittsburgh, PA 15224, USA; University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA 15224, USA.
authors.forename: Jerry
authors.initials: J
authors.lastname: Vockley
authors.affiliation: University of Rochester Medical Center, Clinic of Inherited Metabolic Disease, Box 777, Genetics 601, Elmwood Avenue, Rochester, NY 14642-8315, USA.
authors.forename: Chin-To
authors.initials: CT
authors.lastname: Fong
authors.affiliation: BioMarin Pharmaceutical Inc., 105 Digital Drive, Novato, CA 94949, USA.
authors.forename: Joellen
authors.initials: J
authors.lastname: Hunt
authors.affiliation: BioMarin Pharmaceutical Inc., 105 Digital Drive, Novato, CA 94949, USA.
authors.forename: John J
authors.initials: JJ
authors.lastname: Mahoney
authors.affiliation: BioMarin Pharmaceutical Inc., 105 Digital Drive, Novato, CA 94949, USA. Electronic address: JCohen@bmrn.com.
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Cohen-Pfeffer
mesh_terms: D000022:Abortion, Spontaneous / Q000139:chemically induced; D000328:Adult; D001708:Biopterins / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D005260:Female; D006801:Humans; D007752:Obstetric Labor, Premature / Q000139:chemically induced; D010649:Phenylalanine / Q000097:blood*; D017042:Phenylketonuria, Maternal / Q000178:diet therapy / Q000188:drug therapy*; D011247:Pregnancy; D011256:Pregnancy Outcome; D055815:Young Adult
chemical_list: D001708:Biopterins; D010649:Phenylalanine; C003402:sapropterin
keywords: Hyperphenylalaninemia; Maternal PKU syndrome; Phenylalanine; Phenylketonuria; Sapropterin; Tetrahydrobiopterin