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Mol Genet Metab. 2014 May;112(1):9-16. doi: 10.1016/j.ymgme.2014.02.016. Epub 2014 Mar 12.

Sapropterin dihydrochloride use in pregnant women with phenylketonuria: an interim report of the PKU MOMS sub-registry.

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Washington University School of Medicine, One Children's Place, NWT 9th Floor, St. Louis, MO 63110, USA.
University of Missouri Health Care, One Hospital Drive, University of Missouri, Columbia, MO 65212, USA.
Ann and Robert H. Lurie Children's Hospital of Chicago, 225 E. Chicago Ave., Box #59, Chicago, IL 60611-2605, USA.
Los Angeles County & University of Southern California Medical Center, 1801 Marengo Street, Rm 1G-24, Los Angeles, CA 90033, USA.
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.
University of Rochester Medical Center, Clinic of Inherited Metabolic Disease, Box 777, Genetics 601, Elmwood Avenue, Rochester, NY 14642-8315, USA.
BioMarin Pharmaceutical Inc., 105 Digital Drive, Novato, CA 94949, USA.
BioMarin Pharmaceutical Inc., 105 Digital Drive, Novato, CA 94949, USA. Electronic address:


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.


Hyperphenylalaninemia; Maternal PKU syndrome; Phenylalanine; Phenylketonuria; Sapropterin; Tetrahydrobiopterin

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