We report a 17-year-old female, detected by neonatal screening for hyperphenylalaninemia and diagnosed at the age of 18 months as affected by PTPS deficiency (genotype T67M/K129E). In cerebro-spinal fluid (CSF), homovanillic acid (HVA) and 5 hydroxy-indolacetic acid (5HIAA) were reduced (253 nmol/L and 64 nmol/L respectively). Despite scarce evidence of characteristic extrapyramidal symptoms, our patient presented a stable cognitive deficiency (IQ 52), childhood-onset of anxiety disorders as separation anxiety and social phobia and pubertal onset of obsessive thoughts, hallucinations, odd behaviour and compulsiveness. These psychiatric features followed a fluctuant trend. On two different occasions of psychiatric symptom recrudescence during adolescence, CSF examination showed a normal level of 5HIAA and HVA and very high concentrations of 3-O-methyl-dopa and 5-hydroxy-tryptophan. Sertraline was introduced in augmentation of traditional therapy, with significant regression of symptoms. These findings suggest that normal levels of biogenic amines in CSF may not correspond to symptomatology abatement: normal concentrations of amine metabolites may not reflect neurotransmitter availability and activity at the receptor level.