PKU babies typically appear normal at birth and in the neonatal period. Infants may later exhibit irritability, posturing, increased deep tendon reflexes, a peculiar “mousy” odor, and vomiting. Pale pigmentation develops in hair and skin, and seizures are sometimes present. Phenylalanine accumulates within the first days of life and tyrosine levels tend to be low. Although various phenylalanine metabolites are present, phenylalanine itself appears to be the toxic molecule in PKU. High phenylalanine levels prevent transport of other amino acids across the blood-brain barrier, inhibiting synthesis of key neurotransmitters and disrupting protein synthesis in the brain. This produces severe intellectual disability and white matter disease.
Patients with PKU need to maintain normal, physiological levels of phenylalanine and tyrosine for life. Studies have shown that periods of elevated Phenylalanine affect brain development and function. Newborns diagnosed with PKU should begin dietary treatment as soon as possible. Several commercial PKU formulas and various phenylalanine-restricted foods are available. Phenylalanine (and tyrosine) should be measured on a regular basis to follow dietary control.