Abstract
Patients with the autosomal recessive disorder phenylketonuria (PKU) have elevated phenylalanine levels that impede production of tyrosine, a precursor to dopamine. Lowered dopamine levels lead to a number of deficits, including lowered visual contrast sensitivity (Diamond & Herzberg, 1996; Gramer et al, 2013; Stemerdink et al, 1999). In the present study we measured contrast sensitivity and blood phenylalanine and tyrosine levels on multiple visits in 10 PKU patients, 5 of whom began a course of sapropterin dihydrochloride (Kuvan®), which reduces phenylalanine levels (in some patients). The expectation was that initial contrast sensitivity would correlate with phenylalanine and tyrosine levels, and that in patients who responded well to sapropterin dihydrochloride, reduced phenylalanine levels would correspond to increased contrast sensitivity. Contrast thresholds for each PKU patient and age-matched controls were determined using a four-alternative forced-choice grating discrimination task with an adaptive staircase (the Freiburg Visual Acuity Test, Bach, 1996; 2007) at five spatial frequencies, on multiple visits (1-4 per patient). On Visit 1, prior to sapropterin dihydrochloride treatment, contrast thresholds were an average of 67% higher in PKU patients than in their age-matched controls, but no correlation between performance and phenylalanine or tyrosine levels was detectable. During sapropterin dihydrochloride treatment, however, phenylalanine levels dropped by half, and contrast sensitivity deficits disappeared entirely. Practice also played a role in improvement: threshold elevations were 10% lower on Visit 2 among those patients who had not begun treatment. Control participants displayed a similar degree of improvement on their second visit. Results during treatment suggest that sapropterin hydrochloride may be effective in reducing both phenylalanine levels and corresponding perceptual deficits in PKU patients. The practice effect, however, raises the possibility that only some of the contrast sensitivity deficit in PKU patients is the result of dopamine-related impairments in the retina or visual cortex.
Meeting abstract presented at VSS 2015