Dietary problems of phenylketonuria: effect on CNS transmitters and their possible role in behaviour and neuropsychological function.

Thirty years ago it was observed that the synthesis of serotonin, dopamine and norepinephrine was impaired in untreated phenylketonuria (PKU) as judged either by a decreased concentration in the blood or decreased excretion in the urine of these neurotransmitters, or of their metabolites, 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA). Fifteen years later, when early treatment of PKU with a phenylalanine restricted diet was routinely introduced, an inverse relationship was found between phenylalanine levels and the urinary excretion of dopamine and serotonin. An inverse relationship between blood phenylalanine levels and cerebrospinal fluid (CSF) concentrations of HVA and 5-HIAA has repeatedly been reported during the past 10 years. Recently, the effect of the discontinuation of diet in PKU on the synthesis of dopamine, norepinephrine and serotonin has been examined, and the possible relationship between low levels of these neurotransmitters and impaired performance on neuropsychological tests has been evaluated. In some PKU patients the performance on neuropsychological tests of higher integrative function is impaired after discontinuation of diet, especially when blood phenylalanine values exceed 1200 mumol/L, and the patients often complain of lack of concentration and emotional instability. When these patients return to a 'relaxed' phenylalanine restricted, tyrosine enriched diet, the impaired neuropsychological and behavioural functions appear to be reversible. One mechanism may involve an impaired synthesis of dopamine and serotonin, as the improvement is accompanied by an increase in dopamine and serotonin excretion and a significant increase in CSF concentrations of HVA and 5-HIAA.(ABSTRACT TRUNCATED AT 250 WORDS)