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Contrast sensitivity was assessed in 47 children aged 5.4-9.8 years: 12 with phenylketonuria (PKU), six unaffected siblings and 29 children from the general population. Children with PKU, despite early and continuous treatment and despite phenylalanine (Phe) levels within accepted limits, were impaired across the range of spatial frequencies [1.5-18.0 cycles per degree of visual angle (c.p.d.)]. They were most impaired at the next to the highest spatial frequency, where "group' accounted for 70% of the variance in sensitivity to contrast, controlling for acuity, sex, age and test site. Never, at any spatial frequency, was the contrast sensitivity of any PKU subject better than that of his or her sibling. All subjects were tested under conditions of 20/20 vision, with correction if needed. The mean IQ of PKU subjects was 99; IQ was not significantly related to contrast sensitivity performance. We interpret these findings as support for Diamond's hypothesis that moderately elevated plasma Phe levels (3-5 x normal), combined with reduced plasma tyrosine (Tyr), moderately reduce the levels of Tyr reaching the eye and brain, which adversely affects those dopamine neurons that fire and turn over dopamine most rapidly (the dopamine neurons in the retina and those projecting to prefrontal cortex). This would lead to the deficit in contrast sensitivity found here and to the selective deficit in prefrontal cortex cognitive functions previously reported in PKU children under moderately good dietary control.

Impaired sensitivity to visual contrast in children treated early and continuously for phenylketonuria