Abstract
Phenylketonuria (PKU) is a genetic disorder characterized by impaired ability to metabolize the amino acid phenylalanine (Phe) into tyrosine (Tyr), a precursor to neurotransmitters including dopamine. Dopamine deficiency is proposed to underlie cognitive deficits and reduced contrast sensitivity in PKU. However, consensus has not been reached on the spatial frequencies impacted. Conflicting results may be due to use of a chart-based contrast sensitivity test with poor test-retest reliability or to inclusion of participants with varied blood levels of Phe/Tyr. To assess these possibilities, we used a more rigorous, computer-generated psychophysical test to measure contrast sensitivity in 14 children with PKU (M age = 11.6 years), who had been treated with a phenylalanine-restrictive diet from an early age, and 81 age-matched controls (M age = 11.9 years). Seven children also received sapropterin dihydrochloride (Kuvan®; a drug that may decrease Phe) at some point during the study. Contrast sensitivity was measured with a four-alternative forced-choice orientation discrimination task (Freiburg Visual Acuity Test) at five spatial frequencies (1.5 - 18.0 cpd). A subset of children (9 PKU; 10 control) returned for repeat assessments; four children were receiving Kuvan. Phe/Tyr levels were measured in children with PKU before each assessment. The PKU group (before Kuvan treatment) showed significantly lower contrast sensitivity (47%) at 1.5 cpd compared to controls; no group differences were found at higher spatial frequencies. Kuvan-treated children showed a reduction in Phe/Tyr, and a resolution of the contrast sensitivity deficit. The deficit persisted in children treated with diet alone, although a small improvement was noted. The contrast sensitivity deficit at low spatial frequencies in PKU is consistent with some previous studies, but the lack of deficit at higher spatial frequencies is not. This deficit is dependent on blood levels of Phe/Tyr, and possibly on the choice of contrast sensitivity test.