Speed of decision-making and set-switching: Subtle executive deficits in children with treated phenylketonuria

Phenylketonuria (PKU) is an inborn error of protein metabolism affecting about 1 in 10,000 children in which conversion of dietary phenylalanine into tyrosine is impaired. Unmetabolised phenylalanine accumulates in body tissue and is neurotoxic to the developing organism. The untreated child is almost invariably brain damaged and severely learning disabled. These gross neuropathic effects can be prevented by early implementation of a phenylalanine-restricted diet. Nonetheless, treated children may suffer subtle neuropsychological deficits in the form of mild executive dysfunction, possibly because of depletion of the neurotransmitter dopamine in prefrontal cortex. Dopamine is a downstream metabolite in the phenylalanine pathway but, because of the phenylalanine-tyrosine block, may be in short supply in treated PKU. We investigated the dopamine/executive hypothesis by comparing the performance of 22 early and continuously treated PKU children with controls, matched for non-executive ability, on the test of everyday attention for children. We found the PKU children did not show deranged selective or sustained attention, but were significantly slow on set-switching (creature counting), stop-go (walk/don’t walk), stroop-like (opposite worlds) and target-detection (sky search) tasks. These findings add weight to a growing body of evidence suggesting that rapid decision-making is subtly impaired in PKU, possibly due to prefrontal neurotransmitter insufficiency, and that speeded strategic and choice-reaction tests are particularly sensitive tools for investigating executive dysfunction. How these findings translate into daily domestic and scholastic functioning has yet to be established.