Measurement of neurotransmitter metabolites in the cerebrospinal fluid of phenylketonuric patients under dietary treatment

The plasma Phe levels were averaged over periods of 12 months and were in the age range according to the recommendations for treatment recently reported from the German Working Group for Metabolic Diseases (Burgard et al 1999). Interestingly, plasma tyrosine was below the normal range in four patients, and in the lowest range in the remaining patients. All the examined patients showed low concentrations of neurotransmitter metabolites in CSF. Our data showed a severe deÐ- ciency of dopamine and serotonin metabolites in the central nervous system of phenylketonuric adolescents still on diet. To our knowledge, this is the Ðrst report inwhich a deÐciency of dopamine and serotonin metabolism has been detected in early-treated PKU patients still on diet. Indeed, it was reported that only patients not treated or o† diet showed low levels of CSF HVA and 5-HIAA (Scriver et al 1995). To investigate whether the decrease in dopamine and serotonin metabolites in CSF could be related to neural cell damage or dysfunction, we determined NAA and NAAG concentrations in the CSF of the patients. Both NAA and NAAG are found almost exclusively in neurons (Powels and Frahm 1997). NAA concentrations were normal in all samples (\7.4 kmol/L, normal \7.4, n\25) except one in which NAA was just above normal (patient 4, NAA\9.0 kmol/L); NAAG concentrations were normal in all samples examined (up to 8.7 kmol/L, normal 0.7È12.7, n\25). Our results, even if restricted to a limited number of patients, raise the following issues. (a) PKU needs a careful neurological follow-up during adolescence and adulthood. (b) The question whether long-term dietary treatment can or should be relaxed or discontinued is still unresolved. (c) Diet modiÐcations including di†erent amino acid supplementation (i.e. increased amount of tyrosine) should be considered as an additional treatment in the long-term diet.