MARCH 2022 Question: A two-hour-old male neonate born at 38 weeks’ gestation is being evaluated. His mother is a 22-year-old, gravida 1, para 0 woman with a history of mild phenylketonuria and herpes infection treated with valacyclovir. No active genital lesions were noted at the time of delivery. He was born vaginally with Apgar scores of 8 and 9 at 1 and 5 minutes, respectively. His weight is 2.2. kg (2nd percentile), length 46 cm (5th percentile), and head circumference 33 cm (10th percentile). Physical examination reveals a well-appearing neonate with 2/6 systolic murmur. Of the following, the findings seen in this neonate are MOST likely caused by A.
abnormal maternal phenylalanine level
B.
exposure to valacyclovir
C.
herpes simplex infection
D.
neonatal phenylalanine hydroxylase genotype
ANSWER: A Neonates born to mothers with phenylketonuria (PKU) are at risk for complications related to maternal phenylalanine levels. Neonates born to mothers with PKU are exposed to elevated phenylalanine levels and may develop intrauterine growth restriction, microcephaly, structural cardiac anomalies, and developmental delays. The risk of developing these complications is proportional to maternal serum phenylalanine levels. Phenylketonuria is caused by a defect in phenylalanine hydroxylase resulting in excess serum phenylalanine. It is the most common inherited disease of metabolism related to amino acid metabolism, with an incidence of 0.8 in 100,000 live births. Elevated phenylalanine levels impair myelination and can result in profound neurologic impairment. Management includes dietary restriction of natural proteins supplemented with phenylalanine free amino acid mixtures. In the 1970s, it was thought that dietary restriction was only required during childhood and adolescence. However, more recent data suggest that restriction should continue through adulthood to optimize outcomes. Strict dietary adherence during pregnancy improves neonatal outcomes. Neonates with PKU are often asymptomatic in the neonatal period, with abnormal neurologic findings developing over time. Phenylketonuria is routinely diagnosed on newborn screening performed before hospital discharge. Ideally, neonates diagnosed with PKU should be followed in a center with experience managing inherited diseases of metabolism. Strict adherence to these dietary restrictions is challenging because of the bland taste. In comparison to maternal PKU, phenylalanine hydroxylase deficiency in the fetus does not cause intrauterine growth restriction, because in the situation maternal phenylalanine hydroxylase would maintain normal serum levels of phenylalanine in the growing fetus. If neonates with PKU do not have a phenylalanine restricted diet, they develop neurologic impairment and poor growth. Neonatal PKU typically presents only after enteral feedings have begun. Risk of microcephaly and growth restriction because of herpes infection is unlikely given that this was not a primary herpes infection. Intrauterine exposure to valacyclovir is not associated with growth restriction.