Phenylalanine tolerance in three phenylketonuric women pregnant with fetuses of different genetic PKU status.

Pregnancy management in phenylketonuric women includes continuous dietary control starting before conception, aiming to maintain blood phenylalanine concentrations in a desirable range, irrespective of the fetal genetic PKU status. While the maternal phenylalanine hydroxylase (PAH) genotype will influence metabolic control, an effect of the fetal genetic PKU status on maternal metabolic control during pregnancy has not been described. We monitored three pregnancies of women with classical PKU by dietary protocols of daily phenylalanine intake, phenylalanine blood concentrations, and obstetric care. Patients 1 and 2 carried a heterozygous (not PKU-affected) fetus, while patient 3 was pregnant with a PKU-affected fetus (PAH p.R408W and p.R408W). The expected increase in phenylalanine tolerance during the course of pregnancy was observed in patients 1 and 2 in whom phenylalanine intake could be steadily increased from 400 to 1700 mg/day while phenylalanine blood concentrations remained in the desired range. Gain of body weight was 13.0 and 17.7 kg, respectively. In patient 3, the phenylalanine tolerance did not rise above 600 mg/day, and phenylalanine blood concentrations were above the desired range on several occasions. Caloric intake was therefore encouraged, which led to a weight gain of 20.0 kg. The course of pregnancy was otherwise normal in all three cases, and infants with normal birth weight and head circumference were born. The different phenylalanine tolerance in pregnancies with PKU-affected and non-affected fetuses suggests that PAH genotype and metabolic situation of the fetus influence maternal metabolic control. A phenylalanine tolerance remaining low in the third trimester of pregnancy may indicate fetal PKU.

Intake of major nutrients by women in the Maternal Phenylketonuria (MPKU) Study and effects on plasma phenylalanine concentrations.

BACKGROUND: Women with untreated phenylketonuria (PKU) often have poor reproductive outcomes. OBJECTIVE: We assessed the effects of intakes of major nutrients on plasma phenylalanine concentrations and we measured phenylalanine hydroxylase activity and phenylalanine intakes in pregnant women with PKU. DESIGN: Dietary intakes and plasma phenylalanine concentrations were compared in 4 subject groups defined on the basis of plasma phenylalanine concentrations: group 1 (n = 23), <360 micromol/L by 10 wk gestation and 120-360 micromol/L throughout the remainder of pregnancy; group 2 (n = 46), <600 micromol/L but not <360 micromol/L by 10 wk gestation and 120-600 micromol/L throughout the remainder of pregnancy; group 3 (n = 24), <600 micromol/L by 10 wk gestation but >600 micromol/L at least once thereafter; group 4 (n = 147), never <600 micromol/L. RESULTS: Except in the first trimester, mean intakes of phenylalanine, energy, and fat tended to be greater in group 1 than in the other groups. The mean protein intake of group 1 tended to be greater than that of the other groups. Intakes of protein (P < 0.0001), fat (P < 0.0001), and energy (P < 0.007) were negatively correlated with maternal plasma phenylalanine concentrations. It appeared that genotype did not affect phenylalanine tolerance. CONCLUSIONS: Maternal genotype appeared to have little influence on phenylalanine requirements during the first trimester. Early decline and maintenance of maternal plasma phenylalanine concentrations at <360 micromol/L and mean protein intake greater than the recommended dietary allowance (RDA) with mean energy intake near the RDA resulted in the best reproductive outcomes. Inadequate intakes of protein, fat, and energy may result in elevated plasma phenylalanine concentrations and may contribute to poor reproductive outcomes.