Preventing maternal phenylketonuria (PKU) syndrome: important factors to achieve good metabolic control throughout pregnancy

Carmen Rohde,Christoph Baerwald,Rudolf Georg Ascherl,Christina Heller,Simone Luttat,Kathrin Schönherr,Tina Winkler,Stefanie Rosenbaum-Fabian,Alena Gerlinde Thiele,Monika Joerg-Streller,Ulrike Och,Dinah Lier,Alexandra Jung,Oxana Joos,Skadi Beblo,Sabine Matzgen

doi:10.1186/s13023-021-02108-5

Abstract

BackgroundInsufficient metabolic control during pregnancy of mothers with phenylketonuria (PKU) leads to maternal PKU syndrome, a severe embryo-/fetopathy. Since maintaining or reintroducing the strict phenylalanine (Phe) limited diet in adults with PKU is challenging, we evaluated the most important dietary and psychosocial factors to gain and sustain good metabolic control in phenylketonuric women throughout pregnancy by a questionnaire survey with 38 questions concerning therapy feasibility. Among them, the key questions covered 5 essential items of PKU care as follows: General information about maternal PKU, PKU training, diet implementation, individual metabolic care, personal support. In addition, all participating PKU mothers were asked to estimate the quality of their personal metabolic control of the concluded pregnancies. 54 PKU mothers with 81 pregnancies were approached at 12 metabolic centers in Germany and Austria were included. According to metabolic control, pregnancies of PKU women were divided in two groups: group “ideal” (not more than 5% of all blood Phe concentrations during pregnancy > 360 µmol/l; n = 23) and group “suboptimal” (all others; n = 51).ResultsThe demand for support was equally distributed among groups, concerning both amount and content. Personal support by the direct social environment (partner, family and friends) (“suboptimal” 71% vs “ideal” 78%) as well as individual metabolic care by the specialized metabolic center (both groups around 60%) were rated as most important factors. The groups differed significantly with respect to the estimation of the quality of their metabolic situation (p < 0.001). Group “ideal” presented a 100% realistic self-assessment. In contrast, group “suboptimal” overestimated their metabolic control in 53% of the pregnancies. Offspring of group “suboptimal” showed clinical signs of maternal PKU-syndrome in 27%.ConclusionThe development of training programs by specialized metabolic centers for females with PKU in child bearing age is crucial, especially since those mothers at risk of giving birth to a child with maternal PKU syndrome are not aware of their suboptimal metabolic control. Such programs should provide specific awareness training for the own metabolic situation and should include partners and families.

Highlights

Insufficient metabolic control during pregnancy of mothers with phenylketonuria (PKU) leads to maternal PKU syndrome, a severe embryo-/fetopathy
High maternal Phe concentrations during conception and pregnancy severely impair organogenesis and growth, and maternal PKU syndrome ensues if the mother’s phenylalanine (Phe) concentrations rise above 360 μmol/l during pregnancy
65 mothers with PKU could be approached by the respective treatment centers, 54 were willing to answer the questionnaire for a total number of 81 pregnancies. 7 questionnaires were excluded from analysis: 2 because patients received cofactor treatment with sapropterin dihydrochloride during pregnancy and another 5 where no laboratory data were available

Summary

Introduction

Insufficient metabolic control during pregnancy of mothers with phenylketonuria (PKU) leads to maternal PKU syndrome, a severe embryo-/fetopathy. Pregnancies of PKU women were divided in two groups: group “ideal” (not more than 5% of all blood Phe concentrations during preg‐ nancy > 360 μmol/l; n = 23) and group “suboptimal” (all others; n = 51). Phenylketonuria (PKU) is the most frequent inborn error of amino acid metabolism Untreated, it leads to severe psychomotor retardation. Most women with PKU live a normal life and family planning becomes an important issue In this context, ideal metabolic control during pregnancy is absolutely necessary to prevent maternal PKU syndrome, a severe embryo-/fetopathy. To prevent the birth of a child with maternal PKU syndrome, mothers must keep their plasma Phe concentration between 120 and 360 μmol/l [8,9,10].

Methods

Results

Discussion

Conclusion