Discontinuation of Pegvaliase therapy during maternal PKU pregnancy and postnatal breastfeeding: A case report

Phenylketonuria (PKU) is an inherited metabolic disorder due to phenylalanine hydroxylase (PAH) deficiency resulting in an elevation of Phe [1]. High blood phenylalanine (Phe) is associated with developmental disability, seizures and eczema that are prevented if blood Phe is controlled from infancy within 120–360 μmol/L [2]. The primary treatment for PKU is a Phe-restricted diet that eliminates high protein food and relies on the use of low or Phe-free medical foods. The diet is difficult to follow, and this results in sub-optimal blood Phe, especially in adults [3], with associated adverse neuropsychological outcomes [4]. Consequently, additional non-dietary therapies have been developed. The first of these to be approved was saproterin dihydrochloride,1 a synthetic form of the PAH cofactor tetrahydrobiopterin (BH4). In pharmacological amounts this oral therapy usually serves as adjunctive to diet by enhancing PAH activity in a subpopulation of those with PKU, thereby allowing for a degree of diet liberalization in those patients [5]. A second and more recently approved therapy is pegvaliase pqpz1 (pegvaliase), an injectable enzyme substitution therapy that converts phenylalanine to trans-cinnamic acid and ammonia and can replace dietary therapy in those with PKU who respond to this treatment [6]. Untreated PKU during pregnancy (maternal PKU) results in poor offspring outcomes, including low birth weight, microcephaly, congenital heart defects and developmental disability [7,8]. During clinical trials of pegvaliase, subjects were required to use two forms of birth control and to discontinue the study drug for pregnancy and breastfeeding but the approved label in the U.S. does not contraindicate its use during pregnancy or breastfeeding [9]. Therefore, this decision is left to the judgment of prescribing clinicians. However, there are no human data available regarding the use of pegvaliase during pregnancy or breastfeeding. This case describes the challenges for a woman with PKU who transitioned from pegvaliase therapy and an unrestricted diet to a phe-restricted diet for pregnancy and breastfeeding and the re-introduction of drug therapy after breastfeeding.