Abstract
Sapropterin dihydrochloride (SD) is the first drug treatment for phenylketonuria (PKU), but due to the lack of data, its use in maternal PKU must be undertaken with caution as noted in the FDA and EMEA labels. We collected data from eight pregnancies in PKU women treated with SD and we analysed the phenotypes of these patients, their tetrahydrobiopterin (BH4) responsiveness, the indications for SD treatment, the efficacy (metabolic control, phenylalanine (Phe) tolerance and offspring outcome) and the safety data. Results showed that in the seven patients known to be responsive to BH4, the use of SD during pregnancy was efficient in terms of metabolic control and Phe tolerance. The indications for giving SD included the failure of the low-Phe diet (n = 3), the fact that some of these women had never experienced the low Phe diet (n = 2), one unexpected pregnancy in a woman currently on SD and one pregnancy where the foetus was known to have PKU. The offspring of these seven pregnancies were all normal babies with normal birth measurements and outcomes. No side effect related to SD was observed in these seven cases. In the eighth case, SD was prescribed as a rescue treatment without previous knowledge of the BH4 responsiveness to a woman who was already 8 weeks pregnant without diet. The birth occurred at 33 weeks of gestational age with Potter syndrome (probably related to the absence of metabolic control during the first trimester) and the baby died in the first hours of life. In conclusion, the data presented here provides the first evidence that treatment with pharmacological doses of SD appears to be efficient and safe in women with PKU during pregnancy. Its use should, however, be restricted to those women previously identified to be clear responders to BH4.
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Conflict of interest
Pr Feillet declares speaker honorarium, Board membership and consultancy from Merck Serono. He is the principal investigator of the KAMPER registry supported by Merck Serono.
Pr A Muntau declares speaker honorarium, Board membership and consultancy from Merck Serono.
Pr FG Debray declares no conflict of interest.
Dr Lotz-Haval declares no conflict of interest.
Dr Puchwein-Schwepcke declares no conflict of interest.
Dr Fofou-Caillierez declares no conflict of interest.
Dr van Spronsen declares speaker honorarium, Board membership and consultancy from Merck Serono.
Pr Trefz declares speaker honorarium, Board membership and consultancy from Merck Serono.
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All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000. Informed consent was obtained from all patients.
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Communicating author: F Feillet
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Feillet, F., Muntau, A.C., Debray, FG. et al. Use of sapropterin dihydrochloride in maternal phenylketonuria. A European experience of eight cases. J Inherit Metab Dis 37, 753–762 (2014). https://doi.org/10.1007/s10545-014-9716-5
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DOI: https://doi.org/10.1007/s10545-014-9716-5