Increased Vigilance and Dopamine Synthesis Effected by Large Doses of Tyrosine in Phenylketonuria

In a group of nine patients with classical phenylketonuria (PKU) aged 15 to 24 years, we examined the effect of a phenylalanine-restricted diet on vigilance, as judged by the continuous visual reaction times, and neurotransmitter synthesis, as judged by cerebrospinal fluid (CSF) homo vanillic acid (HVA) and 5-hydroxy-indoleacetic acid (5-HIAA) levels. HVA and 5-HIAA levels decreased significantly with increase in plasma phenylalanine concentration on free diet (p < 0.01 and p < 0.0005, respectively). Vigilance was normal in six patients in whom dietary treatment had been initiated at or before 1 month of age, even at plasma phenylalanine concentrations up to 1877 µmol/1. Vigilance improved on the phenylalanine-restricted diet in six of seven patients with abnormally long reaction times on the free diet. Addition of tyrosine (160 mg/kg per 24 h) to the free diet resulted in an increased HVA-5-HIAA ratio in CSF in the six patients examined. In 14 patients on the free diet supplemented with tyrosine, an improvement in vigilance (reaction times at the 90th percentile) was seen in all 12 patients with values longer than the normal mean (264 ms) (p < 0.001). Tyrosine treatment may be a therapeutic alternative when phenylalanine restriction is impractical.