Neurocognitive evidence for revision of treatment targets and guidelines for phenylketonuria.

[phenylketonuria]

To compare the neurocognitive outcomes of patients with phenylketonuria (PKU ) to determine whether decreasing phenylalanine (Phe ) levels to <240 is preferable to the use of 360 μmol /L as an upper -target Phe level . An additional aim was to establish the influence of biochemical indices other than Phe on neurocognitive outcomes .Patients with PKU (n = 63 ; mean age 10 .8 ± 2 .3 years ) and healthy controls (n = 73 ; mean age 10 .9 ± 2 .2 years ) performed computerized tasks measuring neurocognitive functions (inhibitory control , cognitive flexibility , and motor control ). Lifetime and concurrent blood Phe levels , Phe-to -tyrosine ratio (Phe :Tyr ), and Phe variations were examined in relation to neurocognitive outcomes using nonparametric tests and regression analyses .Patients with PKU with Phe levels ≤240 μmol /L and healthy controls performed equally well . Patients with Phe levels between 240 and 360 μmol /L and ≥360 μmol /L performed more poorly than did controls across tasks . Patients with Phe levels ≤240 μmol /L performed significantly better than patients with levels between 240 and 360 μmol /L on tasks measuring inhibitory control and cognitive flexibility . Absolute Phe levels and Phe variation were the best predictors of motor control , whereas Phe :Tyr were the best predictors of inhibitory control .The results of this study suggest that upper Phe targets should be lowered to optimize neurocognitive outcomes . Moreover , Phe variation and Phe :Tyr appear to be of additional value in treatment monitoring .