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Neuropsychologic studies have shown that even phenylketonuric patients treated early suffer from phenylalanine-related deficits in all age periods, from childhood to adulthood. This study was performed to determine whether phenylketonuric children show specific frontal lobe-dependent deficits when compared with diabetic patients. The comparative study included 42 phenylketonuric patients, 10 to 18 y of age [mean 14.7 (years, months), SD 2.9], and 42 diabetic patients matched for sex, age, and socioeconomic status. Patients were assessed for intelligence quotient (Culture Fair Intelligence Test), information processing (Wisconsin Card Sorting Test, Trail-Making Test), and selective (Stroop task) as well as sustained attention (Test d-2). Phenylketonuric patients had significantly poorer results than the diabetic patients. Within all tests, however, this was due to reduced performance speed, not to deficits in specific functions. Patients did not show deficits in insight and learning. The selection abilities and the sustained attention of the phenylketonuric patients were not impaired. Performance speed and blood phenylalanine levels were negatively correlated. Elevated phenylalanine levels may cause an imbalance in neurotransmitter metabolism. However, this seems to refer to a global neurotoxic effect rather than to specific effects on the dopaminergic system, which would affect specifically the activation of the frontal lobes.

Phenylketonuria: No Specific Frontal Lobe-Dependent Neuropsychological Deficits of Early-Treated Patients in Comparison with Diabetics