Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10833078 | Molecular Genetics and Metabolism | 2014 | 8 Pages |
Abstract
For pregnant women with phenylketonuria (PKU), maintaining blood phenylalanine (Phe) < 360 μmol/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 ± 126.6 μmol/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 ± 300.7 μmol/L (n = 3)] for women exposed to sapropterin prior to pregnancy. Women on sapropterin during pregnancy experienced fewer blood Phe values above the recommended 360 μmol/L threshold. When median blood Phe concentration was < 360 μmol/L throughout pregnancy, 75% (12/16) of pregnancy outcomes were normal compared to 40% (2/5) when median blood Phe was > 360 μmol/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.
Keywords
PKUMedDRAtetrahydrobiopterinBH4OFCLMPPHESAECDCAPGAROccipitofrontal circumferencePAHSapropterinphenylketonurialast menstrual periodMedical Dictionary for Regulatory ActivitiesWorld Health Organizationbody mass indexBMIIdentificationadverse eventSerious adverse eventPhenylalanine hydroxylasePhenylalanineCenters for Disease Control and PreventionHyperphenylalaninemiaWHO
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Authors
Dorothy K. Grange, Richard E. Hillman, Barbara K. Burton, Shoji Yano, Jerry Vockley, Chin-To Fong, JoEllen Hunt, John J. Mahoney, Jessica L. Cohen-Pfeffer,