To begin to study the importance of @entity935 for executive function abilities dependent on prefrontal cortex during early childhood, the present investigation studied @entity1 in whom we predicted reduced @entity935 in prefrontal cortex but otherwise normal brains. These are @entity1 treated early and continuously for the @entity209 @entity814 ( @entity814 ). Untreated @entity814 is the most common biochemical cause of @entity1032 . The root problem is an inability to convert one @entity535 , @entity815 ( @entity815 ), into another, @entity669 (Tyr), the precursor of @entity935 . @entity815 levels in the bloodstream soar; Tyr levels fall. Treatment with a diet low in @entity815 reduces the @entity815 :Tyr imbalance but cannot eliminate it. We hypothesized that the resultant modest elevation in the ratio of @entity815 to Tyr in the blood, which results in slightly less Tyr reaching the brain, uniquely affects the cognitive functions dependent on prefrontal cortex because of the special sensitivity of prefrontally projecting @entity935 neurons to small decreases in Tyr. In a 4-year longitudinal study, we found that @entity814 @entity1 whose plasma @entity815 levels were three to five times normal (6-10 mg/dl) performed worse than other @entity814 @entity1 with lower @entity815 levels, matched controls, their own siblings, and @entity1 from the general population on tasks that required the working memory and inhibitory control abilities dependent on dorsolateral prefrontal cortex. The impairment was as evident in our oldest age range (3 1/2-7 years) as it was in the youngest (6-12 months). The higher a @entity1 's @entity815 level, the worse that @entity1 's performance. @entity1 were more adversely affected than @entity1 . The deficit appears to be selective, affecting principally one neural system, since even @entity814 @entity1 with @entity815 levels three to five times normal performed well on the 13 control tasks. Clinical implications for the treatment of @entity814 and other @entity245 are discussed.

Prefrontal cortex cognitive deficits in @entity1 treated early and continuously for XXXX .

@entity1 :: ('9606', 'Species') :: ['children', 'boys', 'child', 'Girls'] @entity1032 :: ('MESH:D008607', 'Disease') :: ['mental retardation'] @entity935 :: ('MESH:D004298', 'Chemical') :: ['dopamine'] @entity535 :: ('CHEBI:33704', 'Chemical') :: ['amino acid'] @entity245 :: ('MESH:D002658', 'Disease') :: ['neurodevelopmental disorders'] @entity814 :: ('MESH:D010661', 'Disease') :: ['PKU', 'phenylketonuria'] @entity209 :: ('MESH:D008659', 'Disease') :: ['metabolic disorder'] @entity815 :: ('CHEBI:28044', 'Chemical') :: ['Phe', 'phenylalanine'] @entity669 :: ('CHEBI:18186', 'Chemical') :: ['tyrosine']
@entity814 :: (MESH:D010661,Disease) :: ['PKU']
