Format

Send to

Choose Destination
See comment in PubMed Commons below
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.

Author information

1
Washington University School of Medicine, One Children's Place, NWT 9th Floor, St. Louis, MO 63110, USA.
2
University of Missouri Health Care, One Hospital Drive, University of Missouri, Columbia, MO 65212, USA.
3
Ann and Robert H. Lurie Children's Hospital of Chicago, 225 E. Chicago Ave., Box #59, Chicago, IL 60611-2605, USA.
4
Los Angeles County & University of Southern California Medical Center, 1801 Marengo Street, Rm 1G-24, Los Angeles, CA 90033, USA.
5
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.
6
University of Rochester Medical Center, Clinic of Inherited Metabolic Disease, Box 777, Genetics 601, Elmwood Avenue, Rochester, NY 14642-8315, USA.
7
BioMarin Pharmaceutical Inc., 105 Digital Drive, Novato, CA 94949, USA.
8
BioMarin Pharmaceutical Inc., 105 Digital Drive, Novato, CA 94949, USA. Electronic address: JCohen@bmrn.com.

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.

KEYWORDS:

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

PMID:
24667082
DOI:
10.1016/j.ymgme.2014.02.016
[Indexed for MEDLINE]
Free full text
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Support Center