Effects of dietary management of phenylketonuria on long-term cognitive outcome.

BACKGROUND: Phenylketonuria (PKU) is associated with dopaminergic depletion in the dorsolateral prefrontal cortex and abnormalities of myelination. Both mechanisms may lead to deficits in cognitive functioning. Studies of cognitive outcome in children treated with PKU at an early stage have suggested that there are benefits in remaining on diet into adolescence. AIM: To assess the nature and extent of any cognitive deficits in adults treated at an early stage with PKU who had discontinued their diets in adolescence. METHOD: 25 patients (aged 18-38 years) who were diagnosed early and had discontinued their diets in adolescence were compared with 25 adults (aged 18-38 years) with PKU on continuous diet, and with a healthy control group (n = 45). RESULTS: The groups differed significantly on accuracy (p = 0.007) and speed (p = 0.001) of performance on an n-back working memory task and on speed of performance (p = 0.001) on a flanker inhibitory task, but not on flanker accuracy, object alternation learning or perceptual judgement tasks (all p>0.05). The off-diet group performed significantly below the on-diet group on n-back accuracy (p = 0.007) and flanker speed (p = 0.05), and significantly below the control group on n-back speed (p = 0.002) and flanker speed (p = 0.001). CONCLUSION: The findings suggest that although discontinuing diet in adolescence appears disadvantageous compared with remaining on continuous diet, any deficits are relatively subtle.

Executive functioning and speed of processing in phenylketonuria.

Treated phenylketonuria (PKU) has been linked to dopaminergic depletion in the dorsolateral prefrontal cortex, potentially leading to selective executive impairment. White matter abnormalities may lead to generalized slowing of information processing. These 2 hypotheses were evaluated in adults with PKU on a lifelong diet. Those with PKU were significantly slower than the control group regardless of working memory load on an n-back task and marginally slower regardless of trial type (inhibitory or noninhibitory) on a flanker task. There were no significant differences in speed on object alternation learning or perceptual judgment tasks. There were no group differences in accuracy on any task. These findings do not appear consistent with the selective executive hypothesis. A cognitive slowing account may prove more informative in adults with PKU, but more evidence is needed. The findings suggest that continuous dietary management is a fairly successful strategy in terms of cognitive outcome for adults.