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

Abstract

The plasma Phe levels were averaged over periods of 12 months and were in the
\nage range according to the recommendations for treatment recently reported from
\nthe German Working Group for Metabolic Diseases (Burgard et al 1999). Interestingly,
\nplasma tyrosine was below the normal range in four patients, and in the
\nlowest range in the remaining patients. All the examined patients showed low concentrations
\nof neurotransmitter metabolites in CSF. Our data showed a severe deÐ-
\nciency of dopamine and serotonin metabolites in the central nervous system of
\nphenylketonuric adolescents still on diet. To our knowledge, this is the Ðrst report inwhich a deÐciency of dopamine and serotonin metabolism has been detected in
\nearly-treated PKU patients still on diet. Indeed, it was reported that only patients
\nnot treated or o† diet showed low levels of CSF HVA and 5-HIAA (Scriver et al
\n1995).
\nTo investigate whether the decrease in dopamine and serotonin metabolites in
\nCSF could be related to neural cell damage or dysfunction, we determined NAA
\nand NAAG concentrations in the CSF of the patients. Both NAA and NAAG are
\nfound almost exclusively in neurons (Powels and Frahm 1997). NAA concentrations
\nwere normal in all samples (\\7.4 kmol/L, normal \\7.4, n\\25) except one in which
\nNAA was just above normal (patient 4, NAA\\9.0 kmol/L); NAAG concentrations
\nwere normal in all samples examined (up to 8.7 kmol/L, normal 0.7È12.7, n\\25).
\nOur results, even if restricted to a limited number of patients, raise the following
\nissues. (a) PKU needs a careful neurological follow-up during adolescence and
\nadulthood. (b) The question whether long-term dietary treatment can or should be
\nrelaxed or discontinued is still unresolved. (c) Diet modiÐcations including di†erent
\namino acid supplementation (i.e. increased amount of tyrosine) should be considered
\nas an additional treatment in the long-term diet.