Background/Objectives. Maternal phenylketonuria syndrome (MPKUS) is the most serious pregnancy complication of women with phenylketonuria (PKU). High phenylalanine (Phe) levels are indeed embryotoxic for the fetus. A low-Phe diet started before conception and maintained throughout pregnancy ensures optimal blood Phe concentrations (120–360 μmol/L) and pregnancy outcome. Women with unplanned pregnancies are at higher risk of MPKUS and require a rapid and sustained reduction of blood Phe. In this retrospective study, we evaluated the effects of dietary intervention on Phe levels and on the clinical parameters of offspring at birth in a group of patients with PKU. We also describe the fetal outcome of unplanned and untreated mothers with PKU. Methods. The cohort consisted of 13 patients for a total of 22 pregnancies: 16 successful pregnancies and 6 abortions. Pregnancies were divided into three groups: “Planned Pregnancies, PP (n = 5)”, “Unplanned Pregnancies, UP (n = 6)”, and “Unplanned and untreated Pregnancies UT (n = 5)”. Results. Women in the UP group showed higher levels of Phe than women in the PP group, especially during the first trimester. The offspring of the UP group showed no congenital malformations but lower median auxologic parameters at birth compared to those from the PP group, although these were not significantly different. The women in the UT group received the diagnosis of PKU after the birth of offspring with MPKUS. Conclusions. A low-Phe diet is critical to prevent MPKUS, especially when started before conception or no later than the 10th week of gestation. Intensive effort is necessary to avoid unplanned pregnancies and to identify undiagnosed women with PKU at risk of MPKUS.

The mainstay of phenylketonuria treatment is a low protein diet, supplemented with phenylalanine (Phe)-free protein substitutes and micronutrients. Adhering to this diet is challenging, and even patients with good metabolic control who follow the dietary prescriptions in everyday life ignore the recommendations occasionally. The present study explores the ability of slow-release large neutral amino acids (srLNAAs) to prevent Phe increase following a Phe dietary load. Fourteen phenylketonuric patients aged ≥13 years were enrolled in a 6-week protocol. Oral acute Phe loads of 250 and 500 mg were added to the evening meal together with srLNAAs (0.5 gr/kg). Phe and tyrosine were dosed before dinner, 2h-after dinner, and after the overnight fast. After oral Phe loads, mean plasma Phe remained stable and below 600 µmol/L. No Phe peaks were registered. Tyrosine levels significantly increased, and Phe/Tyrosine ratio decreased. No adverse events were registered. In conclusion, a single oral administration of srLNAAs at the dose of 0.5 gr/kg is effective in maintaining stable plasma Phe during acute oral loads with Phe-containing food and may be added to the dietetic scheme in situations in which patients with generally good adherence to diet foresee a higher than prescribed Phe intake due to their commitments.