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

Grange, D. K.; Hillman, R. E.; Burton, B. K.; Yano, S.; Vockley, J.; Fong, C. T.; Hunt, J.; Mahoney, J. J.; Cohen-Pfeffer, J. L.

Mol Genet Metab. 2014 Mar 29; 112(1):9-16


For pregnant women with phenylketonuria (PKU), maintaining blood phenylalanine (Phe)<360mumol/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+/-126.6mumol/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+/-300.7mumol/L (n=3)] for women exposed to sapropterin prior to pregnancy. Women on sapropterin during pregnancy experienced fewer blood Phe values above the recommended 360mumol/L threshold. When median blood Phe concentration was <360mumol/L throughout pregnancy, 75% (12/16) of pregnancy outcomes were normal compared to 40% (2/5) when median blood Phe was >360mumol/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.

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