SUBCLINICAL VISUAL IMPAIRMENT IN PHENYLKETONURIA - A NEUROPHYSIOLOGICAL STUDY (VEP-P) WITH CLINICAL, BIOCHEMICAL, AND NEURORADIOLOGICAL (MRI) CORRELATIONS

During detailed visual function testing, pattern-reversal visual evoke d potentials (VEP), generated by different spatial frequencies (3 c/d, 1 c/d and 0.6 c/d) and visual contrasts (100% and 10%) were recorded in 21 adolescent and young adult phenylketonuric (PKU) patients (11 fe males and 10 males; mean age 14.8 years, range 9-22.8) on and off diet . In 14 of the 21 patients, disease had been detected at neonatal scre ening and in 7 later. Ten age-matched healthy subjects acted as contro ls. Recordings in more than 40% of eyes in the whole group and 30% of eyes in the screening subgroup showed a prolonged P100 latency. All vi sual pattern stimuli elicited a significantly longer P100 latency in P KU patients than in controls. VEP latencies to 3 c/d, 1 c/d and 1 c/d with 10% contrast - but not to 0.6 c/d - were longer in patients off d iet than in patients on diet. No differences were found between VEP la tencies in early- and later-detected subjects. To study the link betwe en biochemical variables and VEP latencies, we envisaged either a line ar relationship between recent exposure to phenylalanine (Phe) and VEP abnormalities or a threshold model considering phenylalanine (Phe) co ncentrations among the factors influencing VEP latencies. The correlat ion analysis detected an association between plasma Phe concentrations and abnormal VEP latencies, predicting that plasma Phe concentrations >901 mu mol/L would prolong VEP latencies to 1c/d; concentrations >87 9 mu mol/L would prolong latencies to 3c/d; and concentrations > 898 m u mol/L would prolong latencies to 1 c/d with 10% contrast. Finally, o ur data confirmed a lack of correlation between white-matter abnormali ties on MRI and abnormal VEP latencies. Our findings suggest that in y oung patients with PKU, prolonged, late exposure to high plasma Phe co ncentrations induces subclinical visual dysfunction. Although our find ings do not allow us to specify the origin of visual system changes in PKU, they favour impairment of the retinal loop as the responsible me chanism.