A woman’s nutritional status before and during pregnancy can affect the health of her progeny. Phenylketonuria (PKU), a rare disorder causing high blood and brain phenylalanine (Phe) concentrations, is associated with neurocognitive disability. Lifelong treatment is mainly dietetic with a Phe-restricted diet, supplemented with a low-Phe protein substitute. Treatment adherence commonly decreases in adolescence, with some adults ceasing dietary treatment. In maternal PKU, elevated blood Phe is harmful to the fetus so a strict Phe-restricted diet must be re-established preconception, and this is particularly difficult to achieve. A woman’s reproductive years introduces an opportunity to adopt healthier behaviours to prepare for successful pregnancies and positive health outcomes for both themselves and their children. Several factors can influence the health status of women with PKU. Political, socioeconomic, and individual food and lifestyle choices affect diet quality, metabolic control, and epigenetics, which then pre-condition the overall maternal health and long-term health of the child. Here, we reflect on a comprehensive approach to treatment and introduce practical recommendations to optimize the wellbeing of women with PKU and the resultant health of their children.

Introduction: In phenylketonuria (PKU) changes in dietary patterns and behaviors in sapropterin-responsive populations have not been widely reported. We aimed to assess changes in food quality, mental health and burden of care in a paediatric PKU sapropterin-responsive cohort. Methods: In an observational, longitudinal study, patient questionnaires on food frequency, neophobia, anxiety and depression, impact on family and burden of care were applied at baseline, 3 and 6-months post successful sapropterin-responsiveness testing (defined as a 30% reduction in blood phenylalanine levels). Results: 17 children (10.8 ± 4.2 years) completed 6-months follow-up. Patients body mass index (BMI) z-scores remained unchanged after sapropterin initiation. Blood phenylalanine was stable. Natural protein increased (p < 0.001) and protein substitute intake decreased (p = 0.002). There were increases in regular cow’s milk (p = 0.001), meat/fish, eggs (p = 0.005), bread (p = 0.01) and pasta (p = 0.011) intakes but special low-protein foods intake decreased. Anxiety (p = 0.016) and depression (p = 0.022) decreased in caregivers. The impact-on-family, familial-social impact (p = 0.002) and personal strain (p = 0.001) lessened. After sapropterin, caregivers spent less time on PKU tasks, the majority ate meals outside the home more regularly and fewer caregivers had to deny food choices to their children. Conclusion: There were significant positive changes in food patterns, behaviors and burden of care in children with PKU and their families after 6-months on sapropterin treatment.

In PKU, the protein requirements are contentious. In 2018, we evaluated the protein intake in patients with PKU. Ninety-nine early treated patients aged 19.3 ± 8.2 years (54% males) were studied. A total of 24 had hyperphenylalaninemia (HPA), 48 mild and 27 classical PKU. All had an annual nutritional status evaluation. A total of 83% were on diet therapy only, and 17% were on diet with tetrahydrobiopterin therapy. Anthropometry, metabolic control and nutritional intake [total protein (TP, g/kg), natural protein (NP, g/kg), protein equivalent from protein substitutes (PE, g/kg)] were collected. TP adequacy (TPA) was calculated as a % of WHO (2007) safe levels of protein intake. Results were compared with the European PKU Guidelines (EPG). The median % contribution NP of TP intake was 53% [31–100]. Most patients (78%) had a TP intake above the EPG recommendations. The median TPA was 171% [146–203], with 79% [51–165] from NP and 84% [0–109] from PE. A TPA of 100–140% was observed in 16 (16%) patients. Only n = 6 (6%) patients had a TPA < 100%. These results emphasize the heterogeneity of PKU. More research is needed to understand the necessity of a single protein recommendation for all, as a ‘one-size-fits-all’ solution might not be appropriate.