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

Background Insufficient 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). Results The 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%. Conclusion The 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.

Phenylketonuria and Hyperphenylalaninemia

Phenylketonuria (PKU) is the prototype treatable genetic disorder and most advanced countries have been performing newborn screening for more than 40 years. Institution of a low-protein diet early in life can reduce the concentration of phenylalanine in the blood and the brain, and prevent the severe learning and behavioral difficulties that were historically associated with PKU. Interestingly, as the brain matures it becomes resistant to the toxic effects of phenylalanine. The effects of high phenylalanine levels on the adult brain are a subject of active research, but, unlike the effects on IQ seen in the first decade of life, they appear to be reversible. The most important effect of high phenylalanine levels in adults is teratogenicity, and in many ways the maternal PKU syndrome is a more devastating disease than PKU itself. Fortunately, maternal PKU syndrome is preventable if women with PKU maintain strict control of phenylalanine levels throughout pregnancy.

Historical Background for the Maternal PKU Syndrome

Objective. To provide information on the history of maternal phenylketonuria. Methods. A review of the literature and personal observations were conducted. Results. Compilation of sequential information about the development of our understanding of maternal PKU was produced. Conclusions. The history of maternal PKU reflects continuous additions to our understanding of this teratogenic syndrome.