The Maternal Phenylketonuria International Study: 1984–2002

Abstract

Objective. The purpose of this report is to review the obstetric medical, psychological, and nutritional aspects and outcome of the women and offspring enrolled in the Maternal Phenylketonuria Study, which was established to assess the efficacy of a phenylalanine (Phe)-restricted diet in preventing the morbidity associated with this disorder. Methods. A total of 382 women with hyperphenylalaninemia (HPA) were enrolled in the study and completed 572 pregnancies. Outcome measures were analyzed with χ2, Fisher exact text, analysis of variance, t test, Wilcoxon nonparametric test, and multiple logistic regression. Outcome measures were stratified according to maternal HPA classification and the time when dietary control was achieved. Results. Optimal birth outcomes occurred when maternal blood Phe levels between 120 and 360 μmol/L were achieved by 8 to 10 weeks of gestation and maintained throughout pregnancy (trimester averages of 600 μmol/L). Mothers with mild HPA achieved similar birth outcomes as mothers who were in control preconceptually and those in control by 8 to 10 weeks of pregnancy. Conclusions. Before conception, counseling and early entrance into a prenatal care program is essential in achieving optimal fetal outcome in women with HPA. The achievement of pre- and periconceptional dietary control with a Phe-restricted diet significantly decreased morbidity in the offspring of women with HPA.

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

“…Gaining and maintaining good metabolic control while planning and during pregnancy is the most important factor for women with PKU who wish to give birth to healthy children. Constant blood Phe concentrations < 360 µmol/l are the best prevention of maternal PKU syndrome [4,6,8,9,16]. However, adolescents and adults with PKU are often not compliant to the prescribed diet, irrespectively of being male or female [17][18][19][20].…”

“…However, adolescents and adults with PKU are often not compliant to the prescribed diet, irrespectively of being male or female [17][18][19][20]. Programs to help women with PKU to achieve sufficient metabolic control during pregnancy have been demanded for decades [8,21,22]. Attempts include home visitation programs [13] hospitalization during pregnancy [14], or accompanying psychotherapy [15], all with inconclusive results.…”

“…7 Centre for Inborn Metabolic Disorders, Department of Neuropediatrics, Jena University Hospital, Jena, Germany. 8 Clinic for Pediatrics, Inherited Metabolic Disorders, Medical University Innsbruck, Innsbruck, Austria. 9 Clinic for Pediatrics, University Magdeburg, Magdeburg, Germany.…”

“…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. To prevent the birth of a child with maternal PKU syndrome, mothers must therefore keep their plasma Phe concentration between 120 and 360 µmol/l [8][9][10]. Unplanned pregnancies should be strictly avoided.…”

A Low-Phenylalanine-Containing Whey Protein Hydrolysate Stimulates Osteogenic Activity through the Activation of p38/Runx2 Signaling in Osteoblast Cells

“…Phenylketonuria (PKU) is a recessively inherited disorder caused by the mutation of the gene coding for phenylalanine hydroxylase (PAH, EC 1.14.16.1), and it results in the inability to catalyze phenylalanine (Phe) into tyrosine [ 1 ]. If an untreated typical PKU patient (BH 4 deficiency) fails to control Phe, the excessive Phe and its metabolites would accumulate in blood and tissues, causing irreversible neurological damage and mental retardation [ 2 ]. The dietary nitrogen requirements of PKU individuals should be met through low-protein diets and Phe-free medical foods [ 3 ].…”